Aflatoxin B1 (AFB1) is a potent mycotoxin that has been shown to induce cardiac damage in rats. In the present study, we investigated the dose-dependent cardioprotective effect of Eggelepanth Skin Ethanol Extract (ESEE) against AFB1-induced cardiac damage in rats, focusing on the cardiac biomarkers lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and brain natriuretic peptide (BNP). Rats were orally administered AFB1 for 28 days to induce cardiac toxicity, and ESEE was co-administered with AFB1 at doses of 200, 400, and 600 mg/kg body weight. The results showed that AFB1 administration caused a significant increase in the levels of LDH, CK-MB, and BNP, as well as lipid peroxidation and inflammatory cytokines in the heart tissues. However, co-administration of ESEE at all doses significantly reduced the levels of LDH, CK-MB, and BNP, as well as lipid peroxidation and inflammatory cytokines in the AFB1-treated rats. Histological examination of the heart tissues showed that AFB1 caused structural damage and inflammation, which were attenuated by ESEE treatment at all doses. The protective effect of ESEE may be attributed to its antioxidant and anti-inflammatory properties, as demonstrated by the significant reduction in oxidative stress markers and pro-inflammatory cytokines in the ESEE-treated rats. These findings suggest that ESEE may be a promising cardioprotective agent against AFB1-induced cardiac damage in rats, and the dose-dependent effect warrants further investigation..