•Divaricatic acid exhibited schistosomicidal effect against adult S. mansoni.•Motility changes were observed in S.mansoni at all concentrations after 24 hours.•Tegumentary damages were caused by the divaricatic acid in Schistosoma mansoni.•No cytotoxicity was observed on PBMC exposed to divaricatic acid after 72h. In this study we evaluated the in vitro effect of divaricatic acid against coupled worms of Schistosoma mansoni. The schistosomicidal effect was evaluated through the bioassay of motility and mortality, cellular viability of the worms and ultrastructural analysis through Scanning Electron Microscopy. To evaluate the cytotoxicity of divaricatic acid, a cell viability assay was performed with human peripheral blood mononuclear cells. Divaricatic acid proved effect against S. mansoni after 3 hours of exposure. At the end of 24 h the concentrations of 100 - 200 μM presented lethality to the worms. Motility changes were observed at sublethal concentrations. The IC50 obtained by the cell viability assay for S. mansoni was 100.6 μM (96.24 - 105.2 μM). Extensive damage to the worm's tegument was observed such as peeling, erosion, bubbles, edema, damage and loss of tubercles and spines, fissures and tissue ruptures. No cytotoxicity was observed in human peripheral blood mononuclear cells. This report provides data showing the schistosomicidal effect of divaricatic acid on S. mansoni, causing death, motile changes and ultrastructural damage to worms. In addition, divaricatic acid was shown to be non-toxic to human peripheral blood mononuclear cells at concentrations effective on S. mansoni. Display omitted