Preventive effects of hydroalcoholic extract of fruit pulp of Eugenia jambolana (HEEJ) on isoproterenol (ISP)-induced myocardial damage in rats were evaluated. Rats were pre-treated with HEEJ (100, 200, and 400 mg/kg) daily for 30 days. ISP (85 mg/kg bw) was administered on the 28th and 29th days at an interval of 24 h. Ischemic control group exhibited significant increases in oxidative stress parameters, markers of inflammation, cardiac damage markers, and apoptotic markers. Oral pre-treatment with HEEJ (100, 200, and 400 mg/kg bw) provided cardioprotective activity by decreasing levels of malondialdehyde, cardiac markers (serum glutamate oxaloacetate transaminase, creatine kinase-myocardial band, cardiac troponin I), and markers of inflammation (interleukin-6, C-reactive protein, and tumor necrosis factor alpha); and increased levels of superoxide dismutase and reduced glutathione. HEEJ (400 mg/kg bw) was found to exert significantly greater effects in comparison to HEEJ (100 and 200 mg/kg bw). Apoptotic marker Bcl-2 was increased, while Bax was decreased in pre-treated rats, which was further confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The present study provides evidence that pre-treatment with HEEJ attenuates oxidative stress, apoptosis and improves cardiac architecture in ISP-induced rats and, hence, is cardioprotective.