Background: The aim was to investigate the antioxidant effects of lycopene and caffeine in rats exposed to renal ischemia/reperfusion (IR) injury. Materials and Methods: Following right renal nephrectomy, 60 minutes of ischemia followed by 60 minutes of reperfusion were performed in 200-250 gram Wistar albino rats used in the study. 30 minutes before ischemia, lycopene (5 mg/kg), caffeine (50 mg/kg), lycopene (5 mg/kg) + caffeine (50 mg/kg) were administered intraperitoneally to the rats. After the experiment, 4 ml of blood and left kidney were taken from the rats. Tissue malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and serum creatinine activities were measured biochemically and light microscopy findings were evaluated histologically. Results: When MDA levels are compared; Although the MDA level of the IR+Lycopene group was lower than the IR group, no significance was observed. When IR+Lycopene and IR+Caffeine groups are compared; The MDA level of the IR+Lycopene group is higher than the IR+ Caffeine group. In the IR+Caffeine group; A statistically significant increase was observed in serum creatinine compared to the IR+Lycopene+Caffeine group. Although SOD and GSH-Px were higher in the antioxidant groups compared to the IR group, no statistically significant difference was observed. When compared with ischemia-reperfusion group, histopathological damage was found to be significantly lower than in the other groups. It was found that Lycopene and Caffeine reduced apoptosis, tubular dilatation, tubular epithelium degeneration, glomerular shrinkage, desquame epithelium and proteinous cast amount significantly. Conclusions: While lycopene has high antioxidant efficiency when compared with caffeine, lycopene and caffeine have protective effect against renal ischemia reperfusion injury.