The goal of this study is to evaluate the effect of Balanites aegyptiaca methanolic extract fruits as an alternative sustainable source of anthelmintic drugs, on adult gastrointestinal multiple drug resistant helminthes and clarify how B. aegyptiaca fruits directly affect helminthes. To fulfill this study, three hundred and fifty sheep reared in a private farm, in Giza Governorate, had been subjected to clinical investigation. Of them, fifty five severely affected sheep had been isolated relying on their clinical history of multiple anthelmintic resistances, to be slaughtered. The post mortem examination revealed that the animals had a mixed infection with Haemonchus contortus, Moniezia expansa and Fasciola gigantica. Light and scanning electron microscopic studies were undertaken to evaluate changes in body wall of these adult worms following 24 h exposure to methanolic extract of B. aegyptiaca fruits utilizing concentrations of 10, 50, 100, 200 and 400 µg/ml. The main target organ that was highly affected was the body wall, whose damage was observed by light and scanning electron microscopic studies. These alterations occurred in particular sequences in response to Balanites extract concentration, initiated with swelling that was even disrupted, resulting in sloughing off cuticle or tegument, and finally exposure and disruption of basal lamina. This damage would induce disturbance for many of the physiological processes associated with the body wall, especially nutrition and immunoprotection. This plant may offer an opportunity for a new natural anthelmintic and an alternative source for the control of such infectious disease in sheep.