Background: Fascioliasis is a worldwide parasitic infection caused by a food-borne trematode called Fasciola, and Fasciola infection has been reported in more than 80 countries. Recently, the WHO has presented a roadmap for overlooked diseases from 2021 to 2030, which aims to increase the prevention and control of overlooked different diseases such as Fascioliasis. Methods: Our main objective was to conduct a systematic review aiming to summarize recent knowledge on the antiparasitic compounds against human fascioliasis. A keyword search was performed in PubMed, Web of Science, to gather relevant literature published between the 17th of April 1992 and the 23rd October 2022. A total of 329 records were initially retrieved, with 28 full-text articles retained for the qualitative synthesis. Results: Up to now, various antiparasitic drugs have been used to treat human fascioliasis, the most important of which are: Triclabendazole, Albendazole and Bithionol, Praziquantel, Emetine and Dehydroemetine, Mebendazole in combination with Metronidazole and Nitazoxanide, Chloroquine, Hexylresorcinol. From the past to the present, natural herbal medicines have traditionally been used in most countries to treat various parasitic diseases in humans and animals so that these are known as active anthelmintic phytochemicals such as Artemisinin, Mirazid, Plumbagin, Lycium chinense. Conclusion: Although Triclabendazole is an effective and useful drug of choice for the treatment of human fascioliasis, but due to the gradual resistance of fasciolas to Triclabendazole, further research is needed to find new drugs. Despite many advances in antiparasitic compounds used against human fascioliasis, a number of integrated control measures should be implemented as strong management strategies for fascioliasis.