Protein carbonyls are formed as a consequence of the oxidative modification of proteins by reactive oxygen species and are commonly used as a marker of protein oxidation in cells and tissues. Melatonin has free radical scavenging ability besides its classical role as a hormonal signaling agent. Curcumin, a phytochemical, has a wide variety of biological actions including anti-inflammatory and antioxidative. In the present study, the effects of melatonin and curcumin on age-related carbonyl content of liver in mice were investigated. Young (1 month) and aged (18 month) were administered with melatonin (10 mg/kg body weight) and curcumin (90 mg/kg body weight) in dimethyl sulfoxide intraperitoneally. Livers were excised from each experimental group and processed. The level of protein carbonylation was assessed spectrophotometrically and further confirmed by Western blotting analysis. Protein carbonyls of liver have been found to be significantly higher in 18-month-old mice as compared to 1-month-old mice. The carbonyl content in 1- and 18-month-old mice decreases significantly upon administrations of melatonin and curcumin. This study thus suggests that the formation of protein carbonyls in the liver of the aging mice can be prevented by the antioxidative effects of melatonin and curcumin, which may provide health benefits in aging animals.