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.

A number of drugs have been used in control fasciolosis in animals. Drugs differ in their efficacy, mode of action, price, and viability. Fasciolicides (drugs against Fasciola spp.) fall into five main chemical groups:

- Halogenated phenols: bithionol (Bitin), hexachlorophene (Bilevon), nitroxynil (Trodax)

- Salicylanilides: closantel (Flukiver, Supaverm), rafoxanide (Flukanide, Ranizole)

- Benzimidazoles: triclabendazole (Fasinex), albendazole (Vermitan, Valbazen), mebendazol (Telmin), luxabendazole (Fluxacur)

- Sulphonamides: clorsulon (Ivomec Plus)

- Phenoxyalkanes: diamphenetide (Coriban)

Triclabendazole (Fasinex) is considered as the most common drug due to its high efficacy against adult as well as juvenile flukes. Triclabendazole is used in control of fasciolosis of livestock in many countries. Nevertheless, long-term veterinary use of triclabendazole has caused appearance of resistance in "F. hepatica". In animals, triclabendazole resistance was first described in Australia, later in Ireland and Scotland and more recently in the Netherlands. Considering this fact, scientists have started to work on the development of new drug. Recently, a new fasciolicide was successfully tested in naturally and experimentally infected cattle in Mexico. This new drug is called 'Compound Alpha' and is chemically very similar to triclabendazole.

Countries where fasciolosis in livestock was repeatedly reported:

- Europe: UK, Ireland, France, Portugal, Spain, Switzerland, Italy, Netherlands, Germany, Poland

- Asia: Turkey, Russia, Thailand, Iraq, Iran, China, Vietnam, India, Nepal, Japan, Korea, Philippines

- Africa: Kenya, Zimbabwe, Nigeria, Egypt, Gambia, Morocco

- Australia and the Oceania: Australia, New Zealand

- Americas:United States, Mexico, Cuba, Peru, Chile, Uruguay, Argentina, Jamaica, Brazil

On September 8, 2007, Veterinary officials in South Cotabato, Philippines said that laboratory tests on samples from cows, carabaos, and horses in the province's 10 towns and lone city showed the level of infection at 89.5%, a sudden increase of positive cases among large livestock due to the erratic weather condition in the area. They must be treated forthwith to prevent complications with surra and hemorrhagic septicemia diseases. Surra already affected all barangays of the Surallah town.