LC50 of menadione (MEN) against S. mansoni adult worms in vitro was 10.49 ± 1.02 μM at 24 h. MEN induced alterations on tegument and organelles of S. mansoni adult worms in vitro. MEN increased superoxide anion levels in S. mansoni adult worms in vitro. MEN reduced the number of worms and egg formation in S. mansoni-infected mice in vivo. Above effects of MEN compared reasonably well to currently used drug, praziquantel.