The purpose of the current literature is to examine the protective properties of resveratrol (RSV) and gamma-glutamylcysteine (γ-GC) against hepatic injury induced by Azathioprine (AZA) that may have a favorable impact on using resveratrol and/ or gamma-glutamylcysteine with immunosuppressant drugs therapy. The study duration was 4 weeks; fifty Male Wister Albino Rats were classified into 5 groups: control group: and rats were orally treated with normal saline. AZA group, Rats were taken AZA orally at 10 mg/kg. RSV group, rats had oral administration of AZA along with IP injection of RSV; 8ml/Kg, GC group, rats had oral administration of AZA and γ-GC; 100mg/Kg, combination group, rats had oral administration of AZA with IP injection of RSV; 8ml/Kg and γ-GC; 100mg/Kg after 2 h post-injection for 4 weeks. The results indicate that AZA treatment increases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, decreases antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) and depleted hepatic microRNA-122 (miR-122) referred to hepatic injury. Administration of RSV/ γ-GC separately or together modulates levels of liver enzymes and protective hepatic tissue. γ-GC reduced the degree of histological hepatic damage in rats. The results reveal that co-administration of RSV and/or γ-GC can reduce immunosuppressant drug hepatotoxicity.