In the present study, we tried to investigate the effects of melatonin, a novel antioxidant and a potent free radical scavenger, in stress-induced cerebral, cerebellar, cardiac, and hepatic oxidative damage using microscopic and biochemical analysis. A total of 32 male Wistar albino rats were divided into control, stress, stress + saline, and stress + melatonin groups. The rats from the stress groups were exposed to high stress conditions of starvation, immobilization, and cold exposure. The rats from the stress + melatonin group received melatonin daily at 20 mg/kg body weight intraperitoneally for 7 days. At the end of the experiment, the brain, cerebellum, heart, and liver were rapidly removed. The main histopathological damage scores (MHDSs) of the stress and stress + saline groups were higher than those of control group for all of the organs. The MHDSs of melatonin-administered group were lower than those of stress and stress + saline groups. The main tissue superoxide dismutase activities of the stress + melatonin group were even higher than those of the control group in the cerebellum and liver, and main tissue catalase activities of the stress + melatonin group were even higher than those of control group in all of the organs. As a conclusion, we found melatonin very effective in reducing stress-induced organ damage by inhibiting lipid peroxidation and supporting the cellular antioxidant defense system.