In schistosome-infected mice, treatment with ZnO-NPs declined brain oxidative stress parameters, with glutathione and catalase activity considerably enhanced. The therapy, also significantly decreased the levels of nitrite/nitrate, malondialdehyde, and reactive oxygen. ZnO-NPs treatment also improved the neuro-schistosomiasis-related brain histopathological impairment and restored the DNA laddering profile. Here, CAT is linked to schistosomiasis.