the target of this research was to investigate the effect of Balanities aegyptiaca fruit aqueous extract (200 mg/kg BW), alone or in combination with Praziquantel PZQ (300 mg/kg BW) on some biochemical, parasitological, liver histopathology and immunohistochemical parameters in mice infected with Schistosoma mansoni. Results showed that treatment of S. mansoni-infected mice with B. aegyptiaca alone or in combination with PZQ significantly reduced the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as compared to that of the S. mansoni-infected mice group. Treatment of S. mansoni-infected mice with B. aegyptiaca or PZQ and their combination led to a significant reduction in the activity of malondialdehyde (MDA) as compared with the infected control group. While a significant elevation was observed in the activities of antioxidant enzymes glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and nitric oxide (NO) compared with the infected. Results revealed that the diameter and number of egg granuloma were significantly condensed after treatment of S. mansoni-infected mice with B. aegyptiaca, PZQ or their combination in hepatic and intestinal tissue. The histopathological alterations observed in the liver of S. mansoni-infected mice were remarkably recovered after B. aegyptiaca treatments. The reduction in angiogenesis was mostly observed in the group receiving the combination of B. aegyptiaca and PZQ. The alterations in vascular endothelial growth factor (VEGF) expression were significantly less in the liver sinusoids. Overall, B. aegyptiaca significantly inhibited the liver and intestinal damage accompanied by schistosomiasis. It demonstrated potent antioxidant and immunoprotective activities. This study advises that B. aegyptiaca can be considered promising for the development of a complementary and/or alternative against schistosomiasis.