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 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.

Medications that are used to kill roundworms are called ascaricides. Those recommended by the World Health Organization for ascariasis are: albendazole, mebendazole, levamisole and pyrantel pamoate. Other effective agents include tribendimidine and nitazoxanide. Pyrantel pamoate may induce intestinal obstruction in a heavy worm load. Albendazole is contraindicated during pregnancy and children under two years of age. Thiabendazole may cause migration of the worm into the esophagus, so it is usually combined with piperazine.

Piperazine is a flaccid paralyzing agent that blocks the response of Ascaris muscle to acetylcholine, which immobilizes the worm. It prevents migration when treatment is accomplished with weak drugs such as thiabendazole. If used by itself, it causes the worm to be passed out in the feces and may be used when worms have caused blockage of the intestine or the biliary duct.

Corticosteroids can treat some of the symptoms, such as inflammation.

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 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.

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 some cases with severe infestation the worms may cause bowel obstruction, requiring emergency surgery. The bowel obstruction may be due to all the worms or twisting of the bowel. During the surgery the worms may be manually removed.

The recommended treatment for people outside the United States is albendazole combined with ivermectin. A combination of diethylcarbamazine and albendazole is also effective. Side effects of the drugs include nausea, vomiting, and headaches. All of these treatments are microfilaricides; they have no effect on the adult worms. While the drugs are critical for treatment of the individual, proper hygiene is also required.

Different trials were made to use the known drug at its maximum capacity in absence of new drugs. In a study from India, it was shown that a formulation of albendazole had better anti-filarial efficacy than albendazole itself.

In 2003, the common antibiotic doxycycline was suggested for treating elephantiasis. Filarial parasites have symbiotic bacteria in the genus "Wolbachia", which live inside the worm and seem to play a major role in both its reproduction and the development of the disease. This drug has shown signs of inhibiting the reproduction of the bacteria, further inducing sterility.

Clinical trials in June 2005 by the Liverpool School of Tropical Medicine reported an eight-week course almost completely eliminated microfilaraemia.

Limited access to essential medicine poses a challenge to the eradication of trichuriasis worldwide. Also, it is a public health concern that rates of post-treatment re-infection need to be determined and addressed to diminish the incidence of untreated re-infection. Lastly, with mass drug administration strategies and improved diagnosis and prompt treatment, detection of an emergence of antihelminthic drug resistance should be examined.

Mass Drug Administration (preventative chemotherapy) has had a positive effect on the disease burden of trichuriasis in East and West Africa, especially among children, who are at highest risk for infection.

Filarial diseases in humans offer prospects for elimination by means of vermicidal treatment. If the human link in the chain of infection can be broken, then notionally the disease could be wiped out in a season. In practice it is not quite so simple, and there are complications in that multiple species overlap in certain regions and double infections are common. This creates difficulties for routine mass treatment because people with onchocerciasis in particular react badly to treatment for lymphatic filariasis.

Inclusion of NTDs into initiatives for malaria, HIV/AIDS, and tuberculosis, as well as integration of NTD treatment programs, may have advantages given the strong link between these diseases and NTDs. Some neglected tropical diseases share common vectors (sandflies, black flies, and mosquitos). Both medicinal and vector control efforts may be combined.

A four-drug rapid-impact package has been proposed for widespread proliferation. Administration may be made more efficient by targeting multiple diseases at once, rather than separating treatment and adding work to community workers. This package is estimated to cost US$0.40 per patient. When compared to stand-alone treatment, the savings are estimated to be 26–47%. While more research must be done in order to understand how NTDs and other diseases interact in both the vector and the human stages, safety assessments have so far produced positive results.

Many neglected tropical diseases and other prevalent diseases share common vectors, creating another opportunity for treatment and control integration. One such example of this is malaria and lymphatic filariasis. Both diseases are transmitted by the same or related mosquito vectors. Vector control, through the distribution of insecticide treated nets, reduces the human contact with a wide variety of disease vectors. Integrated vector control may also alleviate pressure on mass drug administration, especially with respect to rapidly evolving drug resistance. Combining vector control and mass drug administration deemphasizes both, making each less susceptible to resistance evolution.

Biotechnology companies in the developing world have targeted neglected tropical diseases due to need to improve global health.

Mass drug administration is considered a possible method for eradication, especially for lymphatic filariasis, onchocerciasis, and trachoma, although drug resistance is a potential problem. According to Fenwick, Pfizer donated 70 million doses of drugs in 2011 to eliminate trachoma through the International Trachoma Initiative. Merck has helped The African Programme for the Control of Onchocerciasis (APOC) and Oncho Elimination Programme for the Americas to greatly diminished the effect of Onchocerciasis by donating ivermectin. Merck KGaA pledged to give 200 million tablets of praziquantel over 10 years, the only cure for schistosomiasis. GlaxoSmithKline has donated two billion tablets of medicine for lymphatic filariasis and pledged 400 million deworming tablets per year for five years in 2010. Johnson & Johnson has pledged 200 million deworming tablets per year. Novartis has pledged leprosy treatment, EISAI pledged two billion tablets to help treat lymphatic filariasis.