Human schistosomiasis, caused by trematode worms of the genus Schistosoma, is one of the most significant neglected tropical diseases, affecting more 200 million individuals worldwide and praziquantel is the only available drug to treat this neglected disease. Arctiin is a lignan obtained from Arctium lappa (Asteraceae) with antiinflammatory and antiproliferative activities. Our purpose was to investigate the in vitro and in vivo schistosomicidal activities of arctiin in mice infected with S. mansoni. Arctiin (200 and 100 μM) caused mortality, tegumental alterations, and reduction of motor activity of adult worms of S. mansoni in culture. Oral administration of a single dose of arctiin (25 mg/kg) on day 45 of infection did not reduce worm burden or cause any alteration in the analyzed parameters when compared to infected untreated mice. On the other hand, intraperitoneal treatment with arctiin (50 mg/kg) was able to reduce the hepatic granuloma volume by 20% in comparison to infected untreated mice. In addition, after intraperitoneal administration of arctiin in mice it was shown by HPLC analysis that arctiin was present in murine plasma. More studies should be conducted to verify the possible mechanism of action on inflammatory components present in granuloma formation.