Background: Malvidin (alvidin-3-glucoside) is a polyphenol that belongs to the class of natural anthocyanin, which is abundantly found in red wines, colored fruits, and the skin of red grapes. Therefore, the current investigation was intended to evaluate the effect of malvidin against myocardial infarction induced by isoproterenol in the rats. Material/Methods: The cardioprotective effects was assessed by determining the effect of malvidin on the activities of endogenous antioxidants - catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH) - and on the levels of lipid peroxidation and serum marker enzymes. The serum levels of IL-6 and TNF-alpha were also determined using an enzyme-linked immunosorbent assay (ELISA) kit. Result: The present study demonstrated a significant cardioprotective effect of malvidin by restoring the defensive activities of endogenous antioxidants - catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH) - and by reducing the levels of lipid peroxidation and serum marker enzymes lactate dehydrogenase (LD) and creatine kinase (CK). Malvidin significantly ameliorated the histopathological changes and impaired mitochondria in the cardiac necrosis stimulated with isoproterenol. Additionally, the results also demonstrated that nuclear translocation of Nrf-2 and subsequent HO-1 expression might be associated with nuclear factor kappa B (NF-kappa B) pathway activation. Conclusions: Our findings suggest that malvidin exerts cardioprotective effects that might be due to possible strong antioxidant and anti-inflammatory activities. Therefore, this study provides the basis for the development of malvidin as a safe and effective treatment of myocardial infarction.