Background Schistosomiasis is a major, but generally overlooked, tropical disease carried by snails of the genus Biomphalaria, which have a large distribution in Egypt. Control of the intermediate host snail is critical in limiting schistosomiasis spread. On the topic of snails’ management, nanotechnology has gained more interest. Results Copper oxide nanoparticles, characterised by transmission electron microscopy and X-ray diffraction, showed a single crystal structure with an average crystallite size around 40 nm by X-ray diffraction and typical transmission electron microscopy (TEM) image. Also, the UV–VIS spectrophotometer displayed a sharp absorption band of CuO NPs. Molluscicidal activity of copper oxide nanoparticles against B. alexandrina snails was observed. Following exposure to CuO NPs (LC50 and LC90 was 40 and 64.3 mg/l, respectively), there was a reduction in the growth and reproductive rates of treated B. alexandrina at the sub-lethal concentrations, as well as, a drop in egg viability. Moreover, CuO NPs exhibited a toxic effect on miracidiae and cercariae of S. mansoni. Scanning electron microscopy (SEM) investigations of the head-foot and mantle of control and treated snails to the sub-lethal concentrations of CuO NPs (LC10 15.6 mg\l–LC25 27.18 mg\l) indicated morphological alterations in the ultrastructure. Conclusions CuO NPs caused a significant effect against the intermediate hosts of S. mansoni and provide a considerable scope in exploiting local indigenous resources as snail molluscicidal agents.