The study examined the protective effects of swertiamarin on rats with experimentally induced myocardial infarction. Three to six week-old male albino Wistar rats were used in this study and experimental myocardial infarction (MI) was induced using isoproterenol. Our results showed that swertiamarin restored the alteration in heart weight, body weight, and heart weight/tibia length ratio of MI-induced rats to basal levels significantly (p < 0.05). Swertiamarin significantly (p < 0.05) restored the levels of cardiac pathophysiological marker creatine kinase (CKMB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine transaminase (ALT), and cardiac troponin I (cTn-1) to near normalcy in MI-induced rats. Levels of oxidative stress markers malondialdehyde (MDA), protein carbonyls (PC), and levels of Vitamin C and Vitamin E were significantly (p < 0.05) reverted to near basal levels in MI-induced rats by swertiamarin. Levels of the antioxidant glutathione (GSH) and antioxidant enzymes which include superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR), and plasma total antioxidant capacity (TAC) were (p < 0.05) brought to near normalcy in MI-induced rats by swertiamarin. Levels of sodium (Na), potassium (k), and calcium (Ca) ATPases were significantly (p < 0.05) restored to near normalcy in MI-induced rats by swertiamarin. Status of pro-inflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and histological aberrations were also significantly (p < 0.05) restored to near normalcy in MI-induced rats by swertiamarin. Together, our results concluded that swertiamarin exerts significant cardioprotective functions in experimental MI in rats.