The use of plant molluscicides for the control of Biomphalaria alexandrina snails is a critical part of schistosomiasis treatment in Egypt. The purpose of this research was to determine the molluscicidal activity of an ethanol extract of Jatropha gossypiifolia leaves against B. alexandrina snails and Schistosoma mansoni free larval stages. The current finding showed that ethanol extract was lethal for B. alexandrina snails, with LC50 at 51mg/ L and LC90 at 66.17 mg/ L. The lethal time for miracidia and cercariae after exposure to LC25 of J. gossypiifolia was 75 and 120 minutes, respectively. In addition, the hemocyte examinations of the treated snails showed that hyalinocyte had ramified membranes with short filopodia, a shrinkage nucleus and vacuoles, while granulocytes had more dense granules, two nuclei, and long filopodia. It caused a significant decrease in the total hemocyte count in all treated snails. Flow cytometry measurements revealed a significant increase in the expression of LC3B as a marker of autophagy at LC25 concentration compared to LC10 and control. In addition, the histopathology of snails exposed to LC25 of plant extract showed a necrotic alteration, which resulted in fiber tissue breakdown, increased empty spaces, the creation of large vacuoles in the head-foot area, and severe damage to gonadal cells. Furthermore, the comet assay indicates that J. gossypiifolia extract caused a genotoxic influence at concentrations LC10 and LC25, where the tail length and the tail moment were significantly increased compared to untreated snails. In conclusion, J. gossypiifolia extract had potent molluscicidal activity against S. mansoni intermediate host and its free larval stages.