Abstract: Nephrotoxicity is a dose-dependent side effect of cisplatin and γ-radiation that limits their clinical usage in the field of cancer treatments. The present study was designed to evaluate the protective effect of gum Arabic (GA) on nephrotoxicity induced in rats by cisplatin and γ-radiation each alone or combined together. Biochemical investigation of kidney function tests, oxidative stress markers, tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) was carried out. Renal trace elements contents (Cu, Zn, Fe, Ca, Mg, Mn, Se and Pt), histopathological examination of kidney tissues and immunohistochemical determination of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were also performed. Results obtained revealed significant elevation in serum urea and creatinine; propagation in lipid peroxidation (MDA); elevation in nitric oxide (NO) concentration, with subsequent elevation of proinflammatory cytokines as TNF-α as well as increased activities of iNOS, eNOS and myeloperoxidase (MPO), parallel to decline in reduced glutathione (GSH) content. Alterations in renal trace elements contents were detected due to treatment with cisplatin and/or γ-radiation. Moreover, histopathological examination of kidney tissue reflected marked injury. Supplemention with GA significantly ameliorated these parameters, indicating its renoprotective and antioxidant properties. In conclusion, pretreatment with GA offers protection against cisplatin and γ -radiation-induced renal cellular damage.