Intestinal ischaemia-reperfusion injury is a common clinical complication in many medical abdominal surgical situations which leads to multiple organ dysfunctions. Azadirachta indica (A.I) is a plant for which many highly beneficial medicinal properties have been ascribed. Therefore, the ameliorative effect of Azadirachta indica against intestinal ischaemia-reperfusion injury induced cardiac and renal oxidative stress was assessed in this study. Sixty rats were grouped into 6 groups with 10 rats each and were humanely cared for using national and institutional guidelines for the management of experimental animals. Rats were anaesthetized with Ketamine (90 mg/kg; i.m.) and Xylazine (10mg/kg; i.m.). A ventral midline laparotomy was performed after shaving and local cleaning with antiseptic solution. To induce intestinal ischemia, the superior mesenteric artery (SMA) was dissected out and carefully clamped with an atraumatic micro-vascular clip. Thereafter, the intestines were returned into the abdomen and the incision was closed temporarily. The clip was removed following 30 minutes of occlusion of the SMA and reperfusion was allowed for 45 minutes. The animals were thereafter sacrificed by cervical dislocation. Group A received corn oil orally for 7 days without intestinal ischaemia-reperfusion injury. Group B underwent intestinal ischaemia-reperfusion injury without any pre-treatment. Groups C, D, E and F were pre-treated with 100 mg/kg A.I, 200 mg/kg A.I, 100 mg/kg vitamin C and 200 mg/kg vitamin C respectively, orally for 7 days and underwent intestinal ischaemia-reperfusion injury on the 8th day. The cardiac and renal hydrogen peroxide (H2O2), serum xanthine oxidase (XO) and myeloperoxidase (MPO) were significantly elevated (p < 0.05) while cardiac and renal reduced glutathione (GSH), glutathione peroxidise (GPx), protein thiol, non-protein thiol and serum nitric oxide (NO) were significantly decreased (p < 0.05) following intestinal ischaemia-reperfusion injury. However, pre-treatment with Azadirachta indica and vitamin C restored the level of cardiac and renal GSH, GPx, protein thiol, non-protein thiol and serum NO and significantly decreased (p < 0.05) the level of cardiac and renal H2O2 , serum MPO and XO. All these findings suggest that pre-treatment with A.I (100 and 200 mg/kg) ameliorated the cardiac and renal injury induced by intestinal ischaemia-reperfusion injury by reducing oxidative stress and increasing the antioxidant defence system.