Arjunic acid (AA) is one of the major active component of Terminalia arjuna known for its health benefits. In the present study, we evaluated cardioprotective potential of Terminalia arjuna extract (TAE) and AA against cobalt chloride (CoCl2)-induced hypoxia damage and apoptosis in rat cardiomyocytes. TAE (50 μg/ml) and AA (8 μg/ml) significantly (p < 0.001) protected H9c2 cells as evidenced by cell viability assays against CoCl2 (1.2 mM)-induced cytotoxicity. TAE and AA pretreatments protected the cells from oxidative damage by decreasing the generation of free radicals (ROS, hydroperoxide, and nitrite levels). TAE and AA pretreatments retained mitochondrial membrane potential by alleviating the rate of lipid peroxidation induced by CoCl2 treatment. TAE and AA pretreatments elevated antioxidant status including phase II antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and total glutathione levels against CoCl2-induced oxidative stress. Further immunoblotting studies confirmed anti-apoptotic effects of TAE and AA by alleviating the phosphorylation of JNK and c-jun and also by regulating protein expression levels of Bcl2, Bax, caspase 3, heat shock protein-70, and inducible nitric oxide synthase. Overall, our results suggest that both the extract and the active component exhibit antioxidant and anti-apoptotic defense against CoCl2-induced hypoxic injury.