Diabetes mellitus leads to an increased risk factor for cardiovascular diseases. Accumulating evidence has demonstrated that high glucose (HG) can promote massive apoptosis in cardiomyocytes. Oxidative stress has been known as main factor responsible for HG-induced apoptosis. Ellagic acid, a natural phenolic compound, exhibits anti-inflammatory, anti-atherogenic, and antioxidant effects. This study was carried out to evaluate the effects of ellagic acid on HG-induced oxidative damage in H9C2 cells. The effect of ellagic acid on the viability of cells was evaluated by the MTT method. The oxidative stress parameters, including levels of malondialdehyde (MDA), glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) activity were also measured. The results indicated that ellagic acid (10 μM and 20 μM) could remarkably enhance the cell viability of H9C2 cells exposed to HG. In addition, ellagic acid significantly improved the levels of intracellular GSH, TAC, and SOD, whereas the levels of MDA were attenuated. These results revealed a protective effect of ellagic acid on HG-induced cytotoxicity, at least partially, by increasing antioxidant activity and preventing oxidative stress.