For patients who do not adequately respond to dietary fiber, osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose can help avoid "cathartic colon" which has been associated with stimulant laxatives. Among the osmotic laxatives, doses of 17–26 g/d of polyethylene glycol have been well studied. Lubiprostone (Amitiza) is a gastrointestinal agent used for the treatment of idiopathic chronic constipation and constipation-predominant IBS. It is well tolerated in adults, including elderly patients. As of July 20, 2006, lubiprostone had not been studied in pediatric patients. Lubiprostone is a bicyclic fatty acid (prostaglandin E1 derivative) that acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements. Unlike many laxative products, lubiprostone does not show signs of tolerance, dependency, or altered serum electrolyte concentration.

Medications may consist of stool softeners and laxatives in IBS-C and antidiarrheals (e.g., opiate, opioid, or opioid analogs such as loperamide, codeine, diphenoxylate) if diarrhea is predominant.

Drugs affecting serotonin (5-HT) in the intestines can help reduce symptoms. On the other hand, many IBS-D patients report that SSRI type medications exacerbate spasms and diarrhea. This is thought to be due to the large number of serotonin receptors in the gut. 5HT3 antagonists such as ondansetron are effective in postinfectious IBS and diarrhea-dominant IBS due to their blockade of serotonin on 5HT3 receptors in the gut; the reason for their benefit is believed to be that excessive serotonin in the gut is thought to play a role in the pathogenesis of some subtypes of IBS. Certain atypical antipsychotic medications, such as clozapine and olanzapine, may also provide relief due to serotonergic properties these agents possess, acting on the same receptors as other medications in this specific category. Benefits may include reduced diarrhea, reduced abdominal cramps, and improved general well-being. Any nausea present may also respond to 5HT3 antagonists owing to their antiemetic properties. Serotonin stimulates the gut motility and so agonists can help constipation-predominant irritable bowel, while antagonists can help diarrhea-predominant irritable bowel. Selective serotonin reuptake inhibitors, SSRIs, frequently prescribed for panic and/or anxiety disorder and depression, affect serotonin in the gut, as well as the brain. The bowels are highly dependent on serotonin for neural communication. "Selective serotonin reuptake inhibitor antidepressants seem to promote global well-being in some patients with irritable bowel syndrome and, possibly, some improvement in abdominal pain and bowel symptoms, but this effect appears to be independent of improved depression. Further research is required."

Mast cells and the compound that they secrete are central to the pathophysiology and implicated in the treatment of IBS; some of the secreted mast cell mediators (and associated receptors) which have been implicated in symptoms of IBS or specific subtypes include: histamine (HRH1, HRH2, HRH3), tryptase and chymase (PAR2), serotonin (5-HT3), PGD2 (DP1). Histamine also causes epithelial secretion of chloride ions and water (associated with secretory diarrhea) by signaling through a receptor or ligand-gated ion channel that has not been identified as of 2015. A 2015 review noted that both H1-antihistamines and mast cell stabilizers have shown efficacy in reducing pain associated with visceral hypersensitivity in IBS; other lower quality studies have also suggested the benefit of these agents for IBS. In a related review on idiopathic mast cell activation syndromes (including IBS), a combined treatment approach using antileukotrienes, H1/H2-antihistamines, and a mast cell stabilizer are suggested.

Symptoms of short bowel syndrome are usually addressed with medication. These include:

- Anti-diarrheal medicine (e.g. loperamide, codeine)

- Vitamin, mineral supplements and L-glutamine powder mixed with water

- H2 blocker and proton pump inhibitors to reduce stomach acid

- Lactase supplement (to improve the bloating and diarrhoea associated with lactose intolerance)

In 2004, the USFDA approved a therapy that reduces the frequency and volume of total parenteral nutrition (TPN), comprising: NutreStore (oral solution of glutamine) and Zorbtive (growth hormone, of recombinant DNA origin, for injection) together with a specialized oral diet. In 2012, an advisory panel to the USFDA voted unanimously to approve for treatment of SBS the agent teduglutide, a glucagon-like peptide-2 analog developed by NPS Pharmaceuticals, who intend to market the agent in the United States under the brandname Gattex. Teduglutide had been previously approved for use in Europe and is marketed under the brand Revestive by Nycomed.

Surgical procedures to lengthen dilated bowel include the Bianchi procedure, where the bowel is cut in half and one end is sewn to the other, and a newer procedure called serial transverse enteroplasty (STEP), where the bowel is cut and stapled in a zigzag pattern. Heung Bae Kim, MD, and Tom Jaksic, MD, both of Children's Hospital Boston, devised the STEP procedure in the early 2000s. The procedure lengthens the bowel of children with SBS and may allow children to avoid the need for intestinal transplantation. As of June 2009, Kim and Jaksic have performed 18 STEP procedures. The Bianchi and STEP procedures are usually performed by pediatric surgeons at quaternary hospitals who specialize in small bowel surgery.

Pain relief is administered concomitantly to the treatment of the primary disease causing tenesmus. Methadone has been shown to be an effective pain-reliever.

Traditionally, nothing by mouth was considered to be mandatory in all cases, but gentle feeding by enteral feeding tube may help to restore motility by triggering the gut's normal feedback signals, so this is the recommended management initially. When the patient has severe, persistent signs that motility is completely disrupted, nasogastric suction and parenteral nutrition may be required until passage is restored. In such cases, continuing aggressive enteral feeding causes a risk of perforating the gut.

Several options are available in the case of paralytic ileus. Most treatment is supportive. If caused by medication, the offending agent is discontinued or reduced. Bowel movements may be stimulated by prescribing lactulose, erythromycin or, in severe cases that are thought to have a neurological component (such as Ogilvie's syndrome), neostigmine. There is also evidence from a systematic review of randomized controlled trials that chewing gum, as a form of 'sham feeding', may stimulate gastrointestinal motility in the post-operative period and reduce the duration of postoperative ileus.

If possible the underlying cause is corrected (e.g. replace electrolytes).

Soluble fiber supplements such as psyllium are generally considered first-line treatment for chronic constipation, compared to insoluble fibers such as wheat bran. Side effects of fiber supplements include bloating, flatulence, diarrhea, and possible malabsorption of iron, calcium, and some medications. However, patients with opiate-induced constipation will likely not benefit from fiber supplements.

Most cases of simple, uncomplicated diverticulitis respond to conservative therapy with bowel rest.

If laxatives are used, milk of magnesia or polyethylene glycol are recommended as first-line agents due to their low cost and safety. Stimulants should only be used if this is not effective. In cases of chronic constipation, polyethylene glycol appears superior to lactulose. Prokinetics may be used to improve gastrointestinal motility. A number of new agents have shown positive outcomes in chronic constipation; these include prucalopride and lubiprostone. Cisapride is widely available in third world countries, but has withdrawn in most of the west. It has not been shown to have a benefit on constipation, while potentially causing cardiac arrhythmias and deaths.

Stem cell therapy is undergoing research as a possible treatment for IBD. A review of studies suggests a promising role, although there are substantial challenges, including cost and characterization of effects, which limit the current use in clinical practice.

If bacterial infection is suspected, antibiotics may be used. Despite being recommended by several guidelines, the use of antibiotics in mild cases of uncomplicated diverticulitis is supported with only "sparse and of low quality" evidence, with no evidence supporting their routine use.

Medical treatment of IBD is individualised to each patient. The choice of which drugs to use and by which route to administer them (oral, rectal, injection, infusion) depends on factors including the type, distribution, and severity of the patient's disease, as well as other historical and biochemical prognostic factors, and patient preferences. For example, mesalazine is more useful in ulcerative colitis than in Crohn's disease. Generally, depending on the level of severity, IBD may require immunosuppression to control the symptoms, with drugs such as prednisone, TNF inhibitors, azathioprine (Imuran), methotrexate, or 6-mercaptopurine.

Steroids, such as the glucocorticoid prednisone, are frequently used to control disease flares and were once acceptable as a maintenance drug. Biological therapy for inflammatory bowel disease, especially the TNF inhibitors, are used in people with more severe or resistant Crohn's disease and sometimes in ulcerative colitis.

Treatment is usually started by administering drugs with high anti-inflammatory effects, such as prednisone. Once the inflammation is successfully controlled, another drug to keep the disease in remission, such as mesalazine in UC, is the main treatment. If further treatment is required, a combination of an immunosuppressive drug (such as azathioprine) with mesalazine (which may also have an anti-inflammatory effect) may be needed, depending on the patient. Controlled release Budesonide is used for mild ileal Crohn's disease.

Ulcerative colitis can be treated with a number of medications, including 5-ASA drugs such as sulfasalazine and mesalazine. Corticosteroids such as prednisone can also be used due to their immunosuppressive and short-term healing properties, but because their risks outweigh their benefits, they are not used long-term in treatment. Immunosuppressive medications such as azathioprine and biological agents such as infliximab and adalimumab are given only if people cannot achieve remission with 5-ASA and corticosteroids. Such treatments are used less commonly due to their possible risk factors, including but not limited to increased risk of cancers in teenagers and adults, tuberculosis, and new or worsening heart failure (these side effects are rare). A formulation of budesonide was approved by the FDA for treatment of active ulcerative colitis in January 2013. The evidence on methotrexate does not show a benefit in producing remission in people with ulcerative colitis. Off-label use of drugs such as ciclosporin and tacrolimus has shown some benefits. Fexofenadine, an antihistamine drug used in treatment of allergies, has shown promise in a combination therapy in some studies. Opportunely, low gastrointestinal absorption (or high absorbed drug gastrointestinal secretion) of fexofenadine results in higher concentration at the site of inflammation. Thus, the drug may locally decrease histamine secretion by involved gastrointestinal mast cells and alleviate the inflammation.

Sulfasalazine has been a major agent in the therapy of mild to moderate ulcerative colitis for over 50 years. In 1977, Mastan S. Kalsi "et al." determined that 5-aminosalicylic acid (5-ASA and mesalazine) was the therapeutically active component in sulfasalazine. Since then, many 5-ASA compounds have been developed with the aim of maintaining efficacy but reducing the common side effects associated with the sulfapyridine moiety in sulfasalazine.

The objective of treatment is to decompress the bowel and to prevent swallowed air from further distending the bowel. If decompression is not achieved or the patient does not improve within 24 hours, a colectomy (surgical removal of all or part of the colon) is indicated. When surgery is required the recommended procedure is a subtotal colectomy with end ileostomy. Fluid and electrolyte replacement help to prevent dehydration and shock. Use of corticosteroids may be indicated to suppress the inflammatory reaction in the colon if megacolon has resulted from active inflammatory bowel disease. Antibiotics may be given to prevent sepsis.

If the condition does not improve, the risk of death is significant. In case of poor response to conservative therapy, a colectomy is usually required.

In the management of small bowel obstructions, a commonly quoted surgical aphorism is: "never let the sun rise or set on small-bowel obstruction" because about 5.5% of small bowel obstructions are ultimately fatal if treatment is delayed. However improvements in radiological imaging of small bowel obstructions allow for confident distinction between simple obstructions, that can be treated conservatively, and obstructions that are surgical emergencies (volvulus, closed-loop obstructions, ischemic bowel, incarcerated hernias, etc.).

A small flexible tube (nasogastric tube) may be inserted through the nose into the stomach to help decompress the dilated bowel. This tube is uncomfortable but does relieve the abdominal cramps, distention, and vomiting. Intravenous therapy is utilized and the urine output is monitored with a catheter in the bladder.

Most people with SBO are initially managed conservatively because in many cases, the bowel will open up. Some adhesions loosen up and the obstruction resolves. However, when conservative management is undertaken, the patient is examined several times a day, and X-ray images are obtained to ensure that the individual is not getting clinically worse.

Conservative treatment involves insertion of a nasogastric tube, correction of dehydration and electrolyte abnormalities. Opioid pain relievers may be used for patients with severe pain. Antiemetics may be administered if the patient is vomiting. Adhesive obstructions often settle without surgery. If the obstruction is complete a surgery is usually required.

Most patients do improve with conservative care in 2–5 days. However, on some occasions, the cause of obstruction may be a cancer and in such cases, surgery is the only treatment. These individuals undergo surgery where the cause of SBO is removed. Individuals who have bowel resection or lysis of adhesions usually stay in the hospital a few more days until they are able to eat and walk.

Small bowel obstruction caused by Crohn's disease, peritoneal carcinomatosis, sclerosing peritonitis, radiation enteritis, and postpartum bowel obstruction are typically treated conservatively, i.e. without surgery.

Except in the most severe cases, ischemic colitis is treated with supportive care. IV fluids are given to treat dehydration, and the patient is placed on bowel rest (meaning nothing to eat or drink) until the symptoms resolve. If possible, cardiac function and oxygenation should be optimized to improve oxygen delivery to the ischemic bowel. A nasogastric tube may be inserted if an ileus is present.

Antibiotics are sometimes given in moderate to severe cases; the data supporting this practice date to the 1950s, although there is more recent animal data suggesting that antibiotics may increase survival and prevent bacteria from crossing the damaged lining of the colon into the bloodstream. The use of prophylactic antibiotics in ischemic colitis has not been prospectively evaluated in humans, but many authorities recommend their use based on the animal data.

Patients being treated supportively are carefully monitored. If they develop worsening symptoms and signs such as high white blood cell count, fever, worsened abdominal pain, or increased bleeding, then they may require surgical intervention; this usually consists of laparotomy and bowel resection.

Medication (to prevent spasms) or Sphincterotomy (surgical procedure to cut the muscle) are the standard treatments for sphincter of Oddi dysfunction. One or the other may be better based on the classification of the condition.

Some causes of bowel obstruction may resolve spontaneously; many require operative treatment. In adults, frequently the surgical intervention and the treatment of the causative lesion are required. In malignant large bowel obstruction, endoscopically placed self-expanding metal stents may be used to temporarily relieve the obstruction as a bridge to surgery, or as palliation. Diagnosis of the type of bowel obstruction is normally conducted through initial plain radiograph of the abdomen, luminal contrast studies, computed tomography scan, or ultrasonography prior to determining the best type of treatment.

Surgical intervention is nearly always required in form of exploratory laparotomy and closure of perforation with peritoneal wash. Occasionally they may be managed laparoscopically.

Conservative treatment including intravenous fluids, antibiotics, nasogastric aspiration and bowel rest is indicated only if the person is nontoxic and clinically stable.

In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others.

Medical treatments include the use of hyperbaric oxygen which has beneficial effects in radiation proctitis or anal damage. Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and vitamin B12 or vitamin D supplements, together with bile acid sequestrants for bile acid diarrhea and possibly antibiotics for small intestinal bacterial overgrowth. Probiotics have all been suggested as another therapeutic avenue.

Endoscopic therapies including argon plasma coagulation have been used for bleeding telangiectasia in radiation proctitis and at other intestinal sites, although there is a rick of perforation. Sucralfate enemas look promising in proctitis.

Surgical treatment may be needed for intestinal obstruction, fistulae, or perforation, which can happen in more severe cases. These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common.

Optimal treatment usually produces significant improvements in quality of life.

Bacterial overgrowth is usually treated with a course of antibiotics although whether antibiotics should be a first line treatment is a matter of debate. Some experts recommend probiotics as first line therapy with antibiotics being reserved as a second line treatment for more severe cases of SIBO. Prokinetic drugs are other options but research in humans is limited. A variety of antibiotics, including tetracycline, amoxicillin-clavulanate, fluoroquinolones, metronidazole, neomycin, cephalexin, trimethoprim-sulfamethoxazole, and nitazoxanide have been used; however, the best evidence is for the use of rifaximin.

A course of one week of antibiotics is usually sufficient to treat the condition. However, if the condition recurs, antibiotics can be given in a cyclical fashion in order to prevent tolerance. For example, antibiotics may be given for a week, followed by three weeks off antibiotics, followed by another week of treatment. Alternatively, the choice of antibiotic used can be cycled.

The condition that predisposed the patient to bacterial overgrowth should also be treated. For example, if the bacterial overgrowth is caused by chronic pancreatitis, the patient should be treated with coated pancreatic enzyme supplements.

Probiotics are bacterial preparations that alter the bacterial flora in the bowel to cause a beneficial effect. Animal research has demonstrated that probiotics have barrier enhancing, antibacterial, immune modulating and anti-inflammatory effects which may have a positive effect in the management of SIBO in humans. "Lactobacillus casei" has been found to be effective in improving breath hydrogen scores after 6 weeks of treatment presumably by suppressing levels of a small intestinal bacterial overgrowth of fermenting bacteria. The multi-strain preparation VSL#3 was found to be effective in suppressing SIBO. "Lactobacillus plantarum", "Lactobacillus acidophilus", and "Lactobacillus casei" have all demonstrated effectiveness in the treatment and management of SIBO. Conversely, "Lactobacillus fermentum" and "Saccharomyces boulardii" have been found to be ineffective. A combination of "Lactobacillus plantarum" and "Lactobacillus rhamnosus" has been found to be effective in suppressing bacterial overgrowth of abnormal gas producing organisms in the small intestine.

Probiotics are superior to antibiotics in the treatment of SIBO. A combination of probiotic strains has been found to produce better results than therapy with the antibiotic drug metronidazole and probiotics have been found to be effective in treating and preventing secondary lactase deficiency and small intestinal bacteria overgrowth in individuals suffering from post-infectious irritable bowel syndrome. Probiotics taken in uncomplicated cases of SIBO can usually result in the individual becoming symptom free. Probiotic therapy may need to be taken continuously to prevent the return of overgrowth of gas producing bacteria. A study by the probiotic yogurt producer Nestlé found that probiotic yogurt may also be effective in treating SIBO with evidence of reduced inflammation after 4 weeks of treatment.

An elemental diet taken for two weeks is an alternative to antibiotics for eliminating SIBO. An elemental diet works via providing nutrition for the individual while depriving the bacteria of a food source. Additional treatment options include the use of prokinetic drugs such as 5-HT4 receptor agonists or motilin agonists to extend the SIBO free period after treatment with an elemental diet or antibiotics. A diet void of certain foods that feed the bacteria can help alleviate the symptoms. For example, if the symptoms are caused by bacterial overgrowth feeding on indigestible carbohydrate rich foods, following a FODMAP restriction diet may help.

Prevention of radiation injury to the small bowel is a key aim of techniques such as brachytherapy, field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy. Medications including ACE inhibitors, statins and probiotics have also been studied and reviewed.

The condition is not usually immediately life-threatening. The intussusception can be treated with either a barium or water-soluble contrast enema or an air-contrast enema, which both confirms the diagnosis of intussusception, and in most cases successfully reduces it. The success rate is over 80%. However, approximately 5–10% of these recur within 24 hours.

Cases where it cannot be reduced by an enema or the intestine is damaged require surgical reduction. In a surgical reduction, the surgeon opens the abdomen and manually squeezes (rather than pulls) the part that has telescoped. If the surgeon cannot successfully reduce it, or the bowel is damaged, they resect the affected section. More often, the intussusception can be reduced by laparoscopy, pulling the segments of intestine apart with forceps.

Acute treatment uses medications to treat any infection (normally antibiotics) and to reduce inflammation (normally aminosalicylate anti-inflammatory drugs and corticosteroids). When symptoms are in remission, treatment enters maintenance, with a goal of avoiding the recurrence of symptoms. Prolonged use of corticosteroids has significant side-effects; as a result, they are, in general, not used for long-term treatment. Alternatives include aminosalicylates alone, though only a minority are able to maintain the treatment, and many require immunosuppressive drugs. It has been also suggested that antibiotics change the enteric flora, and their continuous use may pose the risk of overgrowth with pathogens such as "Clostridium difficile".

Medications used to treat the symptoms of Crohn's disease include 5-aminosalicylic acid (5-ASA) formulations, prednisone, immunomodulators such as azathioprine (given as the prodrug for 6-mercaptopurine), methotrexate, infliximab, adalimumab, certolizumab and natalizumab. Hydrocortisone should be used in severe attacks of Crohn's disease. Biological therapies (biopharmaceuticals) are medications used to avoid long-term steroid use, decrease inflammation, and treat people who have fistulas with abscesses. The monoclonal antibody ustekinumab appears to be a safe treatment option, and may help people with moderate to severe active Crohn's disease. The long term safety and effectiveness of monoclonal antibody treatment is not known. The monoclonal antibody briakinumab is not effective for people with active Crohn's disease.

The gradual loss of blood from the gastrointestinal tract, as well as chronic inflammation, often leads to anemia, and professional guidelines suggest routinely monitoring for this. Adequate disease control usually improves anemia of chronic disease, but iron deficiency may require treatment with iron supplements. Guidelines vary as to how iron should be administered. Besides other, problems include a limitation in possible daily resorption and an increased growth of intestinal bacteria. Some advise parenteral iron as first line as it works faster, has fewer gastrointestinal side effects, and is unaffected by inflammation reducing enteral absorption.

Other guidelines advise oral iron as first line with parenteral iron reserved for those that fail to adequately respond as oral iron is considerably cheaper. All agree that severe anemia (hemoglobin under 10g/dL) should be treated with parenteral iron. Blood transfusion should be reserved for those who are cardiovascularly unstable, due to its relatively poor safety profile, lack of long term efficacy, and cost.