The present work studied the protective effect of Opuntia ficus indica f. inermis fruit juice (OFIJ) against ethanol-induced renal dysfunction in rats. Chronic ethanol administration (3 g/kg b.w) during 12 weeks to Wistar rats, significantly (p < 0.01) increased the serum and kidney malondialdehyde (MDA), the serum contents of urea, creatinine, gamma glutamyl transferase (GGT) and the urinary glucose and protein levels. Whereas, copious ethanol intoxication significantly (p < 0.01) decreased the vitamin E and C levels in serum and kidney tissue as well as the glutathione content (GSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and caused a severe renal histological injuries. Rivalry pre-treatment of ethanol-fed rats with OFIJ (20 and 40 ml/kg b.w., orally), interestingly attenuated the increases in serum and kidney MDA, and enhanced the antioxidant status of the rats by increasing the levels of SOD, CAT, (GSH-Px), GSH and vitamins. The biochemical findings positively corroborate with the amelioration of kidney histological morphology. The results suggest that the renal protective effect of Opuntia ficus indica f. inermis fruit juice (OFIJ) is by attenuating oxidative stress induced by copious ethanol supplement.