Background: Diosgenin, a steroidal saponin from plants, exhibits many biological potentials. Herein, the cardioprotective role of diosgenin is studied. Materials and Methods: The effect of diosgenin, isolated from Dioscorea bulbifera, was studied on hypoxia-reoxygenation (HR) in H9c2 cardiomyoblast cells. The amount of diosgenin in the plant extract was analyzed by high-performance thin layer chromatography using a solvent system comprising of chloroform:methanol:acetic acid:formic acid (13:4.5:1.5:1). Cardioprotection was checked by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Further, the release of lactate dehydrogenase, an enzyme released during cell death was checked. The proteins responsible for cell death (Bax) and cell survival (Bcl-2, hemeoxygenase-1 and Akt) were analyzed using Western blot to check the cardioprotective role of diosgenin. Conclusion:Supplementation of diosgenin mitigates HR injury, thereby exhibiting cardioprotective potential.