Neuro-schistosomiasis can induce neurological symptoms and severe disability. Since the resistance against the chemotherapy "praziquantel" was reported, the aim of the present study was investigating the anti-neuro-schistosomal effects of ZnO nanoparticles and/or L-carnitine (as free radicals scavenger) on schistosome-infected mice, where technology of nanoparticles has come to the forefront in the medical diagnosis and therapeutic drug delivery. In the human body, nanoscale-sized particles can move freely and reveal unique biological, mechanical, electrical, and chemical properties. In the present study, mice were divided into five groups. The first group served as the non-infected control group. Groups II, III, IV, and V were infected with cercariae of Schistosoma mansoni. Mice of groups III and IV were treated with ZnO nanoparticles (5.6mg/kg b. wt.) and L-carnitine (500mg/kg b. wt.), respectively, after 47days post-infection. Finally, mice of the fifth group were injected with ZnO nanoparticles and after 1h, the mice were intraperitoneally injected with L-carnitine once daily for 5days. On day 52, post-infection mice of all groups were cervically decapitated. The treatment of ZnO nanoparticles and/or L-carnitine to schistosome-infected mice decreased brain oxidative stress parameters, where glutathione level and catalase activity were significantly increasedas compared to schistosome-infected group. On the contrary, the treatment decreased nitrite/nitrate, malondialdehyde, and reactive oxygen species levels significantly. In addition, ZnO nanoparticles and/or L-carnitine treatment restored DNA laddering profile and improved the brain histopathological impairments resulting from neuro-schistosomiasis. Finally, the ZnO nanoparticle treatment and the co-treatment of ZnO nanoparticles and L-carnitine revealed anti-neuro-schistosomal effects on the infected mice.