Schistosomiasis mansoni is considered a serious public health problem. As praziquantel is the only drug recommended by the World Health Organization for the treatment and control of schistosomiasis, the development of new drugs is of great significance. In this work, we present the antischistosomal activity of a small set of phthalimido-thiazole derivatives against Schistosoma mansoni. The effects of those derivatives on the viability of larvae juveniles and adult parasites, production and development of eggs, mortality of schistosomules in vitro by counting worms, and stages of eggs of infected animals in acute and chronic phases were evaluated, resulting in the identification of new multistage antischistosomal compounds. Additionally, a study of liver fibrogenesis was released. The phthalimido-thiazole derivatives, compounds 2b-d, 2h-j, had shown activity on schistosomules, achieving 100% mortality even at 5 mg/mL, in the first 24 h. In the chronic phase of schistosomiasis infection, compound 2i promoted a reduction in the number of immature eggs, an increase in the number of non-viable parasite eggs, a reduction in the average number of eggs in the liver and intestine, decrease in the levels of hydroxyproline in the liver, and a reduction in the areas of hepatic fibrosis. This compound also promoted an increase of IL-10 and a reduction in the level of TNF-α in the liver. Accordingly, the phthalimide-thiazole scaffold is a new starting point for the development of multistage compounds that affect S. mansoni viability, egg formation, and production.