This study evaluates the potential protective effect of Myrtus communis leaves buthanolic fraction (MBF) on CoCl2 and H2 O2 -challenged H9c2 cardiomyoblast cells. The identification of the main compounds by LC-ESITOF-MS was assessed. Among the 23 identified molecules (12 ellagitannins, 8 flavonoids, 1 coumarins, 1 anthocyanin and 1 myrtucommulone), 6 have been described for the first time in M. communis. The MBF displayed high amount of total phenolic (151.09mg of GAE/g of DR), flavonoid and tannin contents (21.81 and 49.54 mg of CE/g of DR, resp.) related to its important antioxidant activity such as DPPH (IC50 = 3.3μg/mL) and ABTS (IC50 = 14μg/mL) tests. Otherwise, exposure of cultured H9C2 cells to CoCl2 -simulated hypoxia or H2 O2 -oxidative stress induced over-activity of superoxide dismutase (over 181 %) and Catalase (171 and 500 %, resp.) and decrease in glutathione peroxidase (≈ 48 %) and excess in MDA (≈ 300 %) level. Pretreatment with MBF, attenuated significantly CoCl2 and H2 O2 challenged cardiomyoblasts injury by restoring cell viability (≈ 100 %), oxidative balance and MDA level. These results indicate that WBF can be used as a functional food to reduce the side effects of the oxidative stress and can be therapeutically effective candidate in cardiac ischemic injuries.