The hepatotoxicity and nephrotoxicity of gentamicin has been well documented in humans and animals, although the preventive strategies against it remain to be studied. Sidr Leaves (Zizyphus) is one of the traditional plants used in Egyptian folk medicine for the treatment of different diseases. Reports have revealed that the Sidr Leaves has a significant quantity of phytochemical molecules. The present study was designed to evaluate the possible protective effects of the Sidr Leaves against Gentamicin (GEN) induced oxidative stress and hepatorenal toxicity in rats. Fifty rats were divided into two main groups. The first main group (n=10 rats) served as negative control. The second main group (n=40 rats) were fed on basal diet and were intraperitoneally injected with GEN at (100 mg/Kg body weight) daily for 6 days, Random blood samples were obtained to analyze kidney and liver functions. Then rats were divided into 4 subgroups (10 rats each). One of them was served as a positive control group and the other three subgroups were supplemented with different concentrations of dried Sidr leaves (2.5%, 5%, 7%), respectively for 6 weeks. The results revealed that, following Sidr leaves treatment, renal function markers and serum activities of liver functions significantly improved compared with the GEN group (P < 0.05). Also, Sidr leaves could significantly ameliorate the levels of glucose and attenuate oxidative stress through a decrease of serum malondialdehyde and an increase of superoxide dismutase compared with the GEN group (P < 0.05). Conclusion: the results exhibited that Sidr Leaves have potential effects against GEN -induced hepatorenal toxicity in rat due to its antioxidant and free radical scavenger effects.