The water extract of Omija (Omija) has been used traditionally in the treatment of ischemic damage of the heart and brain tissues. However, little is known about the mechanism by which it rescues myocardial cells from oxidative stress. This study was designed to investigate the protective mechanisms of Omija on H(2)O(2)-induced cytotoxicity in H9c2 cardiomyoblast cells. Treatment with H(2)O(2) resulted in the death of H9c2 cells, characterized by apparent apoptotic features, including fragmentation of the nucleus and an increase in the sub-G(0)/G(1) fraction of the cell cycle. However, Omija markedly suppressed the apoptotic characteristics of H9c2 cells induced by H(2)O(2). In addition, Omija suppressed the features of mitochondrial dysfunction, including changes in the mitochondrial membrane potential and cytosolic release of cytochrome c in H(2)O(2)-treated cells. Treatment with Omija further inhibited the catalytic activation of caspase-9 and caspase-3 and induction of Fas by H(2)O(2). Taken together, these data indicate that the water extract of Omija protects H9c2 cardiomyoblast cells from oxidative stress of H(2)O(2) through inhibition of mitochondrial dysfunction and activation of intrinsic caspase cascades, including caspase-3 and caspase-9.