Background: Two aspects need to be considered for schistosomiasis control: morbidity and transmission. In this context, many soluble substances have been tested and Euphorbia milii latex is one of the most promising Brazilian molluscicides. Phytochemical studies involving simulation of the applicability of this latex on all aquatic forms of the S. mansoni life cycle are rare in the literature. The aim of this work was to evaluate the effect of E. milii latex on S. mansoni in the egg, miracidium and different developmental stages in Biomphalaria glabrata. Methods: The laboratory study was designed to simulate the different forms of exposure of the life cycle stages of S. mansoni to the LC50 of E. milii latex; we tested the exposition from four situations of S. mansoni contact with the latex and observed the exposure on different snails’ infection stage too. All snails were analyzed weekly for cercarial shedding and reproductive biology. Results: The results showed that contact of S. mansoni eggs and miracidia with the LC50 of E. milii negatively influenced the development of the parasite life cycle in the intermediate host, with consequent reduction of cercarial shedding. The exposure of infected snails affected the reproductive biology and cercarial shedding in all intra-mollusk development stages of S. mansoni, but the reduction was greater in the first, fourth, fifth, sixth, seventh and eighth weeks of infection. The LC50 of E. milii latex had toxic action on eggs and miracidia, and the number of cercariae shed by snails during the study period declined by about 80%. Conclusions: We can conclude that the use of natural biodegradable compounds containing low concentrations of substances already characterized as having eco-toxicological potential can be an important tool to reduce the transmission of Schistosomiasis.