For the treatment of individuals, doxycycline is used to kill the "Wolbachia" bacteria that live in adult worms. This adjunct therapy has been shown to significantly lower microfilarial loads in the host, and may kill the adult worms, due to the symbiotic relationship between "Wolbachia" and the worm. In four separate trials over 10 years with various dosing regimens of doxycycline for individualized treatment, doxycycline was found to be effective in sterilizing the female worms and reducing their numbers over a period of four to six weeks. Research on other antibiotics, such as rifampicin, has shown it to be effective in animal models at reducing "Wolbachia" both as an alternative and as an adjunct to doxycycline. However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.

In mass drug administration (MDA) programmes, the treatment for onchocerciasis is ivermectin (trade name: Mectizan); infected people can be treated with two doses of ivermectin, six months apart, repeated every three years. The drug paralyses and kills the microfilariae causing fever, itching, and possibly oedema, arthritis and lymphadenopathy. Intense skin itching is eventually relieved, and the progression towards blindness is halted. In addition, while the drug does not kill the adult worms, it does prevent them for a limited time from producing additional offspring. The drug therefore prevents both morbidity and transmission for up to several months.

Ivermectin treatment is particularly effective because it only needs to be taken once or twice a year, needs no refrigeration, and has a wide margin of safety, with the result that it has been widely given by minimally trained community health workers.

The antibiotic doxycycline is effective in treating lymphatic filariasis. Its drawbacks are that it requires 4 to 6 weeks of treatment and should not be used in young children and pregnant women, which limits its use for mass prevention. The parasites responsible for elephantiasis have a population of endosymbiotic bacteria, "Wolbachia", that live inside the worm. When the symbiotic bacteria of the adult worms are killed by the antibiotic, they no longer provide chemicals which the nematode larvae need to develop, which either kills the larvae or prevents their normal development. This permanently sterilizes the adult worms, which additionally die within 1 to 2 years instead of their normal 10 to 14 year lifespan.

One strategy to control the disease in areas where it is common is the treatment of entire groups of people regardless of symptoms via mass drug administration. This is often done among school-age children and is known as deworming. While testing and treating children who are infected looks like it is effective, there is insufficient evidence to conclude that routine deworming, in the absence of a positive test, improves nutrition, haemoglobin, school attendance or school performance.

For this purpose, broad-spectrum benzimidazoles such as mebendazole and albendazole are the drugs of choice recommended by WHO. These anthelminthics are administered in a single dose are safe, relatively inexpensive, and effective for several months. Mebendazole can be given with a single dose twice a day for three consecutive days. Albendazole is given at a single dose. WHO recommends annual treatment in areas where between 20 and 50% of people are infected, and a twice a year treatment if it is over 50%; and in low risk situation (i.e. less than 20% prevalence) case-by-case treatment. In addition to these, pyrantel pamoate is also equally effective on ascaris. However, it has been reported that albendazole, mebendazole, and pyrantel pamoate are not entirely effective against "T. trichiura" with single oral doses in population-based control.

Other important issues related to the treatment of hookworm are reinfection and drug resistance. It has been shown that reinfection after treatment can be extremely high. Some studies even show that 80% of pretreatment hookworm infection rates can be seen in treated communities within 30–36 months. While reinfection may occur, it is still recommended that regular treatments be conducted as it will minimize the occurrence of chronic outcomes. There are also increasing concerns about the issue of drug resistance. Drug resistance has appeared in front-line anthelmintics used for livestock nematodes. Generally human nematodes are less likely to develop resistance due to longer reproducing times, less frequent treatment, and more targeted treatment. Nonetheless, the global community must be careful to maintain the effectiveness of current anthelmintic as no new anthelmintic drugs are in the late-stage development.

The most common treatment for hookworm are benzimidazoles, specifically albendazole and mebendazole. BZAs kill adult worms by binding to the nematode’s β-tubulin and subsequently inhibiting microtubule polymerization within the parasite. In certain circumstances, levamisole and pyrantel pamoate may be used. A 2008 review found that the efficacy of single-dose treatments for hookworm infections were as follows: 72% for albendazole, 15% for mebendazole, and 31% for pyrantel pamoate. This substantiates prior claims that albendazole is much more effective than mebendazole for hookworm infections. Also of note is that the World Health Organization does recommend anthelmintic treatment in pregnant women after the first trimester. It is also recommended that if the patient also suffers from anemia that ferrous sulfate (200 mg) be administered three times daily at the same time as anthelmintic treatment; this should be continued until hemoglobin values return to normal which could take up to 3 months.

Hookworm infection can be treated with local cryotherapy when the hookworm is still in the skin.

Albendazole is effective both in the intestinal stage and during the stage the parasite is still migrating under the skin.

In case of anemia, iron supplementation can cause relief symptoms of iron deficiency anemia. However, as red blood cell levels are restored, shortage of other essentials such as folic acid or vitamin B12 may develop, so these might also be supplemented.

For "T. b. gambiense" the combination of nifurtimox and eflornithine (NECT) or eflornithine alone appear to be more effective and result in fewer side effects. These treatments may replace melarsoprol when available with the combination being first line. NECT has the benefit of requiring less injections of eflornithine.

Intravenous melarsoprol was previously the standard treatment for second-stage (neurological phase) disease and is effective for both types. Melarsoprol is the only treatment for second stage "T. b. rhodesiense"; however, it causes death in 5% of people who take it. Resistance to melarsoprol can occur.

Broad-spectrum benzimidazoles (such as albendazole and mebendazole) are the first line treatment of intestinal roundworm and tapeworm infections. Macrocyclic lactones (such as ivermectin) are effective against adult and migrating larval stages of nematodes. Praziquantel is the drug of choice for schistosomiasis, taeniasis, and most types of food-borne trematodiases. Oxamniquine is also widely used in mass deworming programmes. Pyrantel is commonly used for veterinary nematodiasis. Artemisinins and derivatives are proving to be candidates as drugs of choice for trematodiasis.

The current treatment for first-stage disease is intravenous or intramuscular pentamidine for "T. b. gambiense" or intravenous suramin for "T. b. rhodesiense".

Treatments for lymphatic filariasis differ depending on the geographic location of the endemic area. In sub-Saharan Africa, albendazole is being used with ivermectin to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. Geo-targeting treatments is part of a larger strategy to eventually eliminate lymphatic filariasis by 2020.

Additionally, surgical treatment may be helpful for issues related to scrotal elephantiasis and hydrocele. However, surgery is generally ineffective at correcting elephantiasis of the limbs. A vaccine is not yet available but in 2013 the University of Illinois was reporting 95% efficacity in testing against "B. malayi" in mice.

Treatment for podoconiosis consists of consistent shoe-wearing (to avoid contact with the irritant soil) and hygiene - daily soaking in water with an antiseptic (such as bleach) added, washing the feet and legs with soap and water, application of ointment, and in some cases, wearing elastic bandages. Antibiotics are used in cases of infection.

There is no vaccine or medicine to treat or prevent Guinea worm disease. Untreated cases can lead to secondary infections, disability and amputations. Once a Guinea worm begins emerging, the first step is to do a controlled submersion of the affected area in a bucket of water. This causes the worm to discharge many of its larvae, making it less infectious. The water is then discarded on the ground far away from any water source. Submersion results in subjective relief of the burning sensation and makes subsequent extraction of the worm easier. To extract the worm, a person must wrap the live worm around a piece of gauze or a stick. The process may take several weeks. Gently massaging the area around the blister can help loosen the worm. This is nearly the same treatment that is noted in the famous ancient Egyptian medical text, the Ebers papyrus from c. 1550 BC. Some people have said that extracting a Guinea worm feels like the afflicted area is on fire. However, if the infection is identified before an ulcer forms, the worm can also be surgically removed by a trained doctor in a medical facility.

Although Guinea worm disease is usually not fatal, the wound where the worm emerges could develop a secondary bacterial infection such as tetanus, which may be life-threatening—a concern in endemic areas where there is typically limited or no access to health care. Analgesics can be used to help reduce swelling and pain and antibiotic ointments can help prevent secondary infections at the wound site. At least in the Northern region of Ghana, the Guinea worm team found that antibiotic ointment on the wound site caused the wound to heal too well and too quickly making it more difficult to extract the worm and more likely that pulling would break the worm. The local team preferred to use something called "Tamale oil" (after the regional capital) which lubricated the worm and aided its extraction.

It is of great importance not to break the worm when pulling it out. Broken worms have a tendency to putrefy or petrify. Putrefaction leads to the skin sloughing off around the worm. Petrification is a problem if the worm is in a joint or wrapped around a vein or other important area.

Use of metronidazole or thiabendazole may make extraction easier, but also may lead to migration to other parts of the body.

In cases of coinfection, combination therapy with ivermectin and diethylcarbamazine is advocated. However coinfection with malaria and HIV, especially among African women, does not respond well to the current combination therapies. It is more pressing for trichuriasis that the recommended drugs fail to provide positive results. A novel drug tribendimidine, which was approved in China by the CCDC for human use in 2004, has been subjected to clinical trials showing that they are highly effective against major human flukes, ascaris (>90% cure rate) and hookworm (>82%); however with low cure rate for whipworm (<37%).

The treatment is determined by where the disease is acquired, the species of "Leishmania", and the type of infection.

For visceral leishmaniasis in India, South America, and the Mediterranean, liposomal amphotericin B is the recommended treatment and is often used as a single dose. Rates of cure with a single dose of amphotericin have been reported as 95%. In India, almost all infections are resistant to pentavalent antimonials. In Africa, a combination of pentavalent antimonials and paromomycin is recommended. These, however, can have significant side effects. Miltefosine, an oral medication, is effective against both visceral and cutaneous leishmaniasis. Side effects are generally mild, though it can cause birth defects if taken within 3 months of getting pregnant. It does not appear to work for "L. major" or "L. braziliensis".

The evidence around the treatment of cutaneous leishmaniasis is poor. A number of topical treatments may be used for cutaneous leishmaniasis. Which treatments are effective depends on the strain, with topical paromomycin effective for "L. major", "L. tropica", "L. mexicana", "L. panamensis", and "L. braziliensis". Pentamidine is effective for "L. guyanensis". Oral fluconazole or itraconazole appears effective in "L. major" and "L. tropica".

A goal of community base efforts is to eliminate microfilariae from the blood of infected individuals in order to prevent transmission to the mosquito. This is primarily accomplished through the use of drugs. The treatment for "B. malayi" infection is the same as for bancroftian filariasis. Diethylcarbamazine (DEC) has been used in mass treatment programs in the form of DEC-medicated salt, as an effective microfilaricidal drug in several locations, including India. While DEC tends to cause adverse reactions like immediate fever and weakness, it is not known to cause any long-term adverse drug effects. DEC has been shown to kill both adult worms and microfilariae. In Malaysia, DEC dosages (6 mg/kg weekly for 6 weeks; 6 mg/kg daily for 9 days) reduced microfilariae by 80% for 18–24 months after treatment in the absence of mosquito control. Microfilariae numbers slowly return many months after treatment, thus requiring multiple drug doses over time in order to achieve long-term control. However, it is not known how many years of mass drug administration is required to eliminate transmission. But currently, there have been no confirmed cases of DEC resistance.

Single doses of two drugs (albendazole-DEC and albendazole-ivermectin) have been shown to remove 99% of microfilariae for a year after treatment and help to improve elephantiasis during early stages of the disease. Ivermectin does not appear to kill adult worms but serves as a less toxic microfilaricide.

Since the discovery of the importance of "Wolbachia" bacteria in the life cycle of "B. malayi" and other nematodes, novel drug efforts have targeted the endobacterium. Tetracyclines, rifampicin, and chloramphenicol have been effective in vitro by interfering with larvae molting and microfilariae development. Tetracyclines have been shown to cause reproductive and embryogenesis abnormalities in the adult worms, resulting in worm sterility. Clinical trials have demonstrated the successful reduction of "Wolbachia" and microfilariae in onchocerciasis and "W. bancrofti" infected patients. These antibiotics, while acting through a slightly more indirect route, are promising antifilarial drugs.

As with many diseases in developing nations, (including trypanosomiasis and malaria) effective and affordable chemotherapy is sorely lacking and parasites or insect vectors are becoming increasingly resistant to existing anti-parasite drugs. Possibly due to the lack of financial return, new drugs are slow to emerge and much of the basic research into potential drug targets takes place in universities, funded by charitable organizations. Product Development Partnerships (PDPs) like Drugs for Neglected Diseases "initiatives" also work on the development of new treatments (combination treatments and new chemical entities) for visceral leishmaniasis.

The traditional treatment is with pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate. Resistance is now common in India, and rates of resistance have been shown to be as high as 60% in parts of Bihar, India.

The treatment of choice for visceral leishmaniasis acquired in India is now Amphotericin B in its various liposomal preparations. In East Africa, the WHO recommended treatment is SSG&PM (sodium stibogluconate and paromomycin) developed by Drugs for Neglected Diseases "initiative" (DNDi)in 2010.

Miltefosine is the first oral treatment for this disease. The cure rate of miltefosine in Phase III clinical trials is 95%; Studies in Ethiopia show that is also effective in Africa. In HIV immunosuppressed people which are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment.

Miltefosine has received approval by the Indian regulatory authorities in 2002, in Germany in 2004 and in U.S.A. in 2014. It is now registered in many countries.

The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbance in the first or second day of treatment (a course of treatment is 28 days) which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalization is avoided, and outpatient distribution of the drug becomes an option, making Miltefosine a drug of choice.

Incomplete treatment has been cited as a major reason of death from visceral leishmaniasis.

The nonprofit Institute for OneWorld Health has adopted the broad spectrum antibiotic paromomycin for use in treating VL; its antileishmanial properties were first identified in the 1980s. A treatment with paromomycin costs about $15 USD. The drug had originally been identified in the 1960s. The Indian government approved paromomycin for sale and use in August 2006.

There are two drugs available, praziquantel and oxamniquine, for the treatment of schistosomiasis. They are considered equivalent in relation to efficacy against "S. mansoni" and safety. Because of praziquantel's lower cost per treatment, and oxaminiquine's lack of efficacy against the urogenital form of the disease caused by "S. haematobium", in general praziquantel is considered the first option for treatment. The treatment objective is to cure the disease and to prevent the evolution of the acute to the chronic form of the disease. All cases of suspected schistosomiasis should be treated regardless of presentation because the adult parasite can live in the host for years.

Schistosomiasis is treatable by taking by mouth a single dose of the drug praziquantel annually.

The WHO has developed guidelines for community treatment based on the impact the disease has on children in villages in which it is common:

- When a village reports more than 50 percent of children have blood in their urine, everyone in the village receives treatment.

- When 20 to 50 percent of children have bloody urine, only school-age children are treated.

- When fewer than 20 percent of children have symptoms, mass treatment is not implemented.

Other possible treatments include a combination of praziquantel with metrifonate, artesunate, or mefloquine. A Cochrane review found tentative evidence that when used alone, metrifonate was as effective as praziquantel.

Another agent, mefloquine, which has previously been used to treat and prevent malaria, was recognised in 2008–2009 to be effective against "Schistosoma".

The standard of care is administration of antifilarial drugs, most commonly Ivermectin or diethyl-carbamazine (DEC). The most efficacious dose in all nematode and parasitic infections is 200 µg/kg of ivermectin. There has also been other various anthelminthic drugs used, such as mebendazole, levamisole, albendazole and thiabendazole. In worst-case scenarios, surgery may be necessary to remove nematodes from the abdomen or chest. However, mild cases usually do not require treatment.

The drug of choice for the treatment of uncomplicated strongyloidiasis is ivermectin. Ivermectin does not kill the "Strongyloides" larvae, only the adult worms, therefore repeat dosing may be necessary to properly eradicate the infection. There is an auto-infective cycle of roughly two weeks in which Ivermectin should be re-administered however additional dosing may still be necessary as it will not kill "Strongyloides" in the blood or larvae deep within the bowels or diverticula. Other drugs that are effective are albendazole and thiabendazole (25 mg/kg twice daily for 5 days—400 mg maximum (generally)). All patients who are at risk of disseminated strongyloidiasis should be treated. The optimal duration of treatment for patients with disseminated infections is not clear.

Treatment of strongyloidiasis can be difficult and "Strongyloides" has been known to live in individuals for decades; even after treatment. Continued treatment is thus necessary even if symptoms resolve.

Because of the high cost of Stromectol, the veterinary formula Ivomec can be used. Government programs are needed to help citizens finance lifelong medication.

Clothes and sheets must be washed with enzyme washing powder and dried on hot daily.

Parasitic worms and nematodes regulate many immune pathways of their host in order to increase their chances of survival. For example, molecules secreted by "Acanthocheilonema vitae" actually limit host effective immune mechanisms. These molecules are called excretory-secretory products. An effective excretory-secretory product released from "Acanthochelionema vitae" is called ES-62, which can affect multiple immune system cell types. ES-62 has anti-inflammatory effects when subjected to mice. The anti-inflammatory effect occurs because of a phosphorylcholine (PC)-containing moiety and signal transduction. More research needs to be completed; however there is some evidence that "Acanthocheilonema vitae" may have anti-inflammatory effects, and should be researched further.

Several drugs are effective for fascioliasis, both in humans and in domestic animals. The drug of choice in the treatment of fasciolosis is triclabendazole, a member of the benzimidazole family of anthelmintics. The drug works by preventing the polymerization of the molecule tubulin into the cytoskeletal structures, microtubules. Resistance of "F. hepatica" to triclabendazole has been recorded in Australia in 1995 and Ireland in 1998.

Praziquantel treatment is ineffective.

There are case reports of nitazoxanide being successfully used in human fasciolosis treatment in Mexico. There are also reports of bithionol being used successfully.

More recently, Mirazid, an Egyptian drug made from myrrh, has been investigated as an oral treatment of trematode-caused ailments including fascioliasis.

Nitazoxanide has been found effective in trials, but is currently not recommended. The life cycle includes freshwater snails as an intermediate host of the parasite.

An infection of "N. americanus" parasites can be treated by using benzimidazoles: albendazole or mebendazole. A blood transfusion may be necessary in severe cases of anemia. Light infections are usually left untreated in areas where reinfection is common. Iron supplements and a diet high in protein will speed the recovery process. In a case study involving 56-60 men with "Trichuris trichiura" and/or "N. americanus" infections, both albendazole and mebendazole were 90% effective in curing "T. trichiura". However, albendazole had a 95% cure rate for "N. americanus", while mebendazole only had a 21% cure rate. This suggests albendazole is most effective for treating both "T. trichiura" and "N. americanus".

Cryotherapy by application of liquid nitrogen to the skin has been used to kill cutaneous larvae migrans, but the procedure has a low cure rate and a high incidence of pain and severe skin damage, so it now is passed over in favor of suitable pharmaceuticals. Topical application of some pharmaceuticals has merit, but requires repeated, persistent applications and is less effective than some systemic treatments.

The highest clearance rates are obtained by combining mebendazole or albendazole with ivermectin. Ivermectin's safety in children under and pregnant women has not yet been established.

People with diarrhea may be treated with loperamide to increase the amount of drug contact with the parasites.

Mebendazole is 90% effective in the first dose, and albendazole may also be offered as an anti-parasitic agent. Adding iron to the bloodstream helps solve the iron deficiency and rectal prolapse. Difetarsone is also an effective treatment.

Cure rates are extremely good with modern treatments, but successful cure results may be of no symptomatic benefit to patients.

If complications of helminthiasis, such as intestinal obstruction occur, emergency surgery may be required. Patients who require non-emergency surgery, for instance for removal of worms from the biliary tree, can be pre-treated with the anthelmintic drug albendazole.

In eye disease, surgical removal is necessary for cysts within the eye itself as treating intraocular lesions with anthelmintics will elicit an inflammatory reaction causing irreversible damage to structural components. Cysts outside the globe can be treated with anthelmintics and steroids. Treatment recommendations for subcutaneous cysticercosis includes surgery, praziquantel and albendazole.