The need for medications to prevent stress ulcer among those in the intensive care unit is unclear. As of 2014, the quality of the evidence is poor. It is unclear which agent is best or if prevention is needed at all. Benefit may only occur in those who are not being fed.

Possible agents include antacids, H2-receptor blockers, sucralfate, and proton pump inhibitors (PPIs). Tentative evidence supports that PPIs may be better than H2 blockers.

Concerns with the use of stress ulcer prophylaxis agents include increased rates of pneumonia and "Clostridium difficile" colitis.

H2 antagonists or proton-pump inhibitors decrease the amount of acid in the stomach, helping with healing of ulcers.

When "H. pylori" infection is present, the most effective treatments are combinations of 2 antibiotics (e.g. clarithromycin, amoxicillin, tetracycline, metronidazole) and a proton-pump inhibitor (PPI), sometimes together with a bismuth compound. In complicated, treatment-resistant cases, 3 antibiotics (e.g. amoxicillin + clarithromycin + metronidazole) may be used together with a PPI and sometimes with bismuth compound. An effective first-line therapy for uncomplicated cases would be amoxicillin + metronidazole + pantoprazole (a PPI).

The principles of management are the same as for the chronic ulcer. The steps of management are similar as in erosive gastritis.

Endoscopic means of treating stress ulceration may be ineffective and operation required. It is believed that shunting of blood away from the mucosa makes the mucous membrane ischaemic and more susceptible to injury.

Treatment of stress ulceration usually begins with prevention. Careful attention to respiratory status, acid-base balance, and treatment of other illnesses helps prevent the conditions under which stress ulcers occur. Patients who develop stress ulcers typically do not secrete large quantities of gastric acid; however, acid does appear to be involved in the pathogenesis of the lesions. Thus it is reasonable either to neutralize acid or to inhibit its secretion in patients at high risk.

In case of severe hemorrhagic or erosive gastritis and stress ulcers, a combination of antacids and H2-blockers may stop active bleeding and prevent re bleeding. In selected patients, either endoscopic therapy or selective infusion of vasopressin into the left gastric artery may help control the hemorrhage.

Antacids are a common treatment for mild to medium gastritis. When antacids do not provide enough relief, medications such as H blockers and proton-pump inhibitors that help reduce the amount of acid are often prescribed.

Cytoprotective agents are designed to help protect the tissues that line the stomach and small intestine. They include the medications sucralfate and misoprostol. If NSAIDs are being taken regularly, one of these medications to protect the stomach may also be taken. Another cytoprotective agent is bismuth subsalicylate.

Several regimens are used to treat "H. pylori" infection. Most use a combination of two antibiotics and a proton pump inhibitor. Sometimes bismuth is added to the regimen.

Diagnostic measures can be used as interventions to help stop bleeding in some cases. Bleeding that occurs due to a neoplasm (cancer growth) can be treated using colonoscopy and clipping, surgical intervention, or other measures, depending on the form and stage of cancer. Similarly, gastric cancer is treated depending on the staging, although typically requires surgical and medical therapy.

The treatment for motility issues, namely constipation, is typically to improve the movement of waste though the GI tract. This is done by using stool softeners (which work by pulling water into the stool while in the colon), addition of fiber to the diet, and use of osmotic laxatives (which help fluid movement through the colon, improving overall motility). Improving a persons gut motility can reduce the straining during defection and decrease the risk of developing of anal fissures. Anal fissures are associated with pain and blood on the toilet paper, and require time for healing. Treatment includes topical nitrates or calcium channel blockers and surgical interventions for chronic or complex cases. Similar to anal fissures, internal hemorrhoids can cause blood on the tissue when wiping, and be felt at the opening of the anus. Treatment options for hemorrhoids can be dependent on whether an underlying cause exists. An anorectal varices related hemorrhoids caused by cirrhosis, however symptomatic treatment often involves removal.

Colitis can be divided into infectious and drug induced, as can the treatment for these conditions. With infectious colitis, treatment is pathogen dependent, and generally requires the use of antibiotics. With drug-induced colitis, treatment typically involves removal of the offending agent, as is the case in NSAID induced PUD, however, removing radiation from a cancer patient is not always practical within a treatment regimen, so medical treatment is the primary mode of treatment.

Structural compromise leading to blood in stool is caused by a variety of conditions, and therefore requires different treatment for each condition. Peptic ulcer disease alone can be divided into multiple causes, but is generally initially controlled primarily with a proton pump inhibitor, with the addition of an H blocker, or in serious cases, requiring surgical intervention. Diverticulitis and diverticulosis require antibiotic treatment, and may require surgical intervention.

Inflammatory bowel disease is also divided into separate conditions, namely ulcerative colitis and Crohn's disease, which have different medical treatment regimens, and may require surgical intervention in more serious conditions.

In most people with peptic ulcer disease, the oedema will usually settle with conservative management with nasogastric suction, replacement of fluids and electrolytes and proton pump inhibitors.

Functional and undifferentiated dyspepsia have similar treatments. Drug therapy decisions are difficult because trials included heartburn in the definition of dyspepsia. This led to the results favoring proton pump inhibitors (PPIs), which are effective for the treatment of heartburn.

Traditional therapies used for this diagnosis include lifestyle modification, antacids, H-receptor antagonists (H2-RAs), prokinetic agents, and antiflatulents. It has been noted that one of the most frustrating aspects of treating functional dyspepsia is that these traditional agents have been shown to have little or no efficacy.

Antacids and sucralfate were found to be no better than placebo in a literature review. H2-RAs have been shown to have marked benefit in poor quality trials (30% relative risk reduction), but only a marginal benefit in good quality trials. Prokinetic agents would empirically seem to work well since delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia. They have been shown in a meta-analysis to produce a relative risk reduction of up to 50%, but the studies evaluated to come to this conclusion used the drug cisapride which has since been removed from the market (now only available as an investigational agent) due to serious adverse events such as torsades, and publication bias has been cited as a potential partial explanation for such a high benefit. Modern prokinetic agents such as metoclopramide, erythromycin and tegaserod have little or no established efficacy and often result in substantial side effects. Simethicone has been found to be of some value, as one trial suggests potential benefit over placebo and another shows equivalence with cisapride. So, with the somewhat recent advent of the proton pump inhibitor (PPI) class of medications, the question of whether these new agents are superior to traditional therapy has arisen.

Currently, PPIs are, depending on the specific drug, FDA indicated for erosive esophagitis, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced ulcer healing and prevention, but not functional dyspepsia. There are, however, evidence-based guidelines and literature that evaluate the use of PPIs for this indication. A helpful chart summarizing the major trials is available from the functional dyspepsia guidelines published in the World Journal of Gastroenterology in 2006.

The treatment for bile reflux is the same as the treatment for acidic reflux. In general, everything that can

reduce acidic reflux can reduce bile reflux. Examples include lifestyle modification, weight reduction, and the avoidance of eating immediately before sleep or being in the supine position immediately after meals. In addition, smoking has been found to be a factor in the development of acidic reflux. Thus, all of these factors should be applied to bile reflux as well.

Likewise, drugs that reduce the secretion of gastric acid (e.g., proton pump inhibitors)

or that reduce gastric contents or volume can be used to treat acidic bile reflux. Because prokinetic drugs increase the motility of the stomach and accelerate gastric emptying, they can also reduce bile reflux. Other drugs that reduce the relaxations of the lower esophageal sphincter, such as baclofen, have also proven to reduce bile reflux, particularly in patients who are refractory to (medically unresponsive to) proton pump inhibitor therapy.

Medications used in managing biliary reflux include bile acid sequestrants, particularly cholestyramine, which disrupt the circulation of bile in the digestive tract and sequester bile that would otherwise cause symptoms when refluxed; and prokinetic agents, to move material from the stomach to the small bowel more rapidly and prevent reflux.

Biliary reflux may also be treated surgically, if medications are ineffective or if precancerous tissue is present in the esophagus.

It is diagnosed and treated endoscopically; however, endoscopic ultrasound or angiography can be of benefit.

Endoscopic techniques used in the treatment include epinephrine injection followed by bipolar or monopolar electrocoagulation, injection sclerotherapy, heater probe, laser photocoagulation, hemoclipping or banding. Alternatively, in patients with refractory bleeding Interventional Radiology may be consulted for an angiogram with subselective embolization.

Treatment of gastric outlet obstruction depends on the cause, but is usually either surgical or medical.

In a "hemodynamically significant" case of hematemesis, that is hypovolemic shock, resuscitation is an immediate priority to prevent cardiac arrest. Fluids and/or blood is administered, preferably by large bore intravenous cannula, and the patient is prepared for emergency endoscopy, which is typically done in theatres. Surgical opinion is usually sought in case the source of bleeding cannot be identified endoscopically, and laparotomy is necessary.

Securing the airway is a top priority in hematemesis patients, especially those with a disturbed conscious level (hepatic encephalopathy in esophageal varices patient.) A cuffed endotracheal tube could be a life saving choice.

The mortality rate for Dieulafoy's was much higher before the era of endoscopy, where open surgery was the only treatment option.

If this is not the case, the patient is generally administered a proton pump inhibitor (e.g. omeprazole), given blood transfusions (if the level of hemoglobin is extremely low, that is less than 8.0 g/dL or 4.5–5.0 mmol/L), and kept NPO, which stands for "nil per os" (Latin for "nothing by mouth", or no eating or drinking) until endoscopy can be arranged. Adequate venous access (large-bore cannulas or a central venous catheter) is generally obtained in case the patient suffers a further bleed and becomes unstable.

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.

Proton pump inhibitors (such as omeprazole and lansoprazole) and histamine H2-receptor antagonists (such as famotidine and ranitidine) are used to slow acid secretion. Once gastric acid is suppressed, symptoms normally improve.

There are many tools for investigating stomach problems. The most common is endoscopy. This procedure is performed as an outpatient and utilizes a small flexible camera. The procedure does require intravenous sedation and takes about 30–45 minutes; the endoscope is inserted via the mouth and can visualize the entire swallowing tube, stomach and duodenum. The procedure also allows the physician to obtain biopsy samples. In many cases of bleeding, the surgeon can use the endoscope to treat the source of bleeding with laser, clips or other injectable drugs.

Pentoxifylline is a useful add on treatment to compression stockings and may also help by itself. It works by reducing platelet aggregation and thrombus formation. Gastrointestinal disturbances were reported as a potential adverse effect.

Sulodexide, which reduces the formation of blood clots and reduces inflammation, may improve the healing of venous ulcers when taken in conjunction with proper local wound care. Further research is necessary to determine potential adverse effects, the effectiveness, and the dosing protocol for sulodexide treatment.

An oral dose of aspirin is being investigated as a potential treatment option for people with venous ulcers. A 2016 Cochrane systematic review concluded that further research is necessary before this treatment option can be confirmed to be safe and effective.

Oral zinc supplements have not been proven to be effective in aiding the healing of venous ulcers, however more research is necessary to confirm these results.

Treatment is cause-related, but also symptomatic if the underlying cause is unknown or not correctable. It is also important to note that most ulcers will heal completely without any intervention. Treatment can range from simply smoothing or removing a local cause of trauma, to addressing underlying factors such as dry mouth or substituting a problem medication. Maintaining good oral hygiene and use of an antiseptic mouthwash or spray (e.g. chlorhexidine) can prevent secondary infection and therefore hasten healing. A topical analgesic (e.g. benzydamine mouthwash) may reduce pain. Topical (gels, creams or inhalers) or systemic steroids may be used to reduce inflammation. An antifungal drug may be used to prevent oral candidiasis developing in those who use prolonged steroids. People with mouth ulcers may prefer to avoid hot or spicy foods, which can increase the pain. Self-inflicted ulceration can be difficult to manage, and psychiatric input may be required in some people.

Internationally, the NPUAP, EPUAP and Pan Pacific Pressure Injury Alliance (Australia, New Zealand, Singapore and Hong Kong) published updated evidence-based clinical practice guidelines in 2014. The guideline was developed by an international team of over 100 clinical specialists and updates the 2009 EPUAP and NPUAP clinical guidelines. The guideline includes recommendations on strategies to treat pressure ulcers, including the use of bed rest, pressure redistributing support surfaces, nutritional support, repositioning, wound care (e.g. debridement, wound dressings) and biophysical agents (e.g. electrical stimulation). Reliable scientific evidence to support the use of many of these interventions, though, is lacking. More research is needed to assess how to best support the treatment of pressure ulcers, for example by repositioning.

The vast majority of people with aphthous stomatitis have minor symptoms and do not require any specific therapy. The pain is often tolerable with simple dietary modification during an episode of ulceration such as avoiding spicy and acidic foods and beverages. Many different topical and systemic medications have been proposed (see table), sometimes showing little or no evidence of usefulness when formally investigated. Some of the results of interventions for RAS may in truth represent a placebo effect. No therapy is curative, with treatment aiming to relieve pain, promote healing and reduce the frequency of episodes of ulceration.

The first line therapy for aphthous stomatitis is topical agents rather than systemic medication, with topical corticosteroids being the mainstay treatment. Systemic treatment is usually reserved for severe disease due to the risk of adverse side effects associated with many of these agents. A systematic review found that no single systemic intervention was found to be effective. Good oral hygiene is important to prevent secondary infection of the ulcers.

Occasionally, in females where ulceration is correlated to the menstrual cycle or to birth control pills, progestogen or a change in birth control may be beneficial. Use of nicotine replacement therapy for people who have developed oral ulceration after stopping smoking has also been reported. Starting smoking again does not usually lessen the condition. Trauma can be reduced by avoiding rough or sharp foodstuffs and by brushing teeth with care. If sodium lauryl sulfate is suspected to be the cause, avoidance of products containing this chemical may be useful and prevent recurrence in some individuals. Similarly patch testing may indicate that food allergy is responsible, and the diet modified accordingly. If investigations reveal deficiency states, correction of the deficiency may result in resolution of the ulceration. For example, there is some evidence that vitamin B12 supplementation may prevent recurrence in some individuals.

Non-elastic, ambulatory, below knee (BK) compression counters the impact of reflux on venous pump failure. Compression therapy is used for venous leg ulcers and can decrease blood vessel diameter and pressure, which increases their effectiveness, preventing blood from flowing backwards. Compression is also used to decrease release of inflammatory cytokines, lower the amount of fluid leaking from capillaries and therefore prevent swelling, and prevent clotting by decreasing activation of thrombin and increasing that of plasmin. Compression is applied using elastic bandages or boots specifically designed for the purpose.

Regarding effectiveness, compression dressings improve healing. It is not clear whether non-elastic systems are better than a multilayer elastic system. Patients should wear as much compression as is comfortable. The type of dressing applied beneath the compression does not seem to matter, and hydrocolloid is not better than simple low adherent dressings. Recently there have been clinical studies on a multi-functional botanical-based ointment in combination with compression therapy in the treatment of difficult-to-heal wounds, including venous leg ulcers.

Intermittent pneumatic compression devices may be used, but it is not clear that they are superior to simple compression dressings.

It is not clear if interventions that are aimed to help people adhere to compression therapy are effective. More research is needed in this field.

If it is caused by esophagitis, in turn caused by an underlying infection, it is commonly treated by treating the infection (typically with antibiotics). In order to open the stricture, a surgeon can insert a bougie – a weighted tube used to dilate the constricted areas in the esophagus. It can sometimes be treated with other medications. For example, an H2 antagonist (e.g. ranitidine) or a proton-pump inhibitor (e.g. omeprazole) can treat underlying acid reflux disease.