Objective: assess possible role of melatonin and garlic in cisplatin-induced AKI in rats. Materials and methods: Forty adult male rats were divided into 5 groups. Group 1: control group. Group 2: cisplatin group (6 mg/kg) IP injection on the 8th day. Group 3: melatonin group (10 mg/kg/day) in saline orally for 12 days+ IP injection of cisplatin on the 8th day. Group 4: garlic group (500mg/kg/day) in saline orally for 12 days+ IP injection of cisplatin on the 8th day. Group 5: received same doses of melatonin and garlic in saline orally +IP injection of cisplatin on the 8th day. By the end of 12th day, blood samples were collected for biochemical analysis. Renal tissue was examined for oxidative stress markers and caspase3. Results: Histopathology and caspase 3 expression revealed marked damage and marked expression of caspase 3 in group 2. The use of melatonin or garlic caused marked reduction of this damage and caspase 3 expression with the best outcome in combined group. Serum creatinine and urea showed a significant increase in group 2 compared to group 1. However, this elevation was significantly reduced by melatonin in group 3 and garlic in group 4 and best outcome in group 5. KIM-1 significantly increased with cisplatin and decreased with treated groups with best outcome in group 5. The oxidative stress showed a significant improvement in group 5 compared to group 2. Conclusion: Melatonin and garlic may protect against cisplatin induced AKI in rats with best outcome in combined group.