Background: Increased oxidative stress and histopathological damage have been implicated in the cardiotoxicity that limits the clinical therapy of cisplatin (CP) as an anti-cancer drug. Objectives: This study aimed to investigate the protective effect of hesperidin (HP) against CP-induced cardiotoxicity in rats. Materials and Methods: Rats were divided into four groups (n = 7/group), and the first group served as the control group. Animals in Group CP and Group CP + HP received a single dose of CP (CP - 7 mg/kg); animals in Group HP and Group CP + HP received 50 mg/kg/day HP with gavage for 14 days. At the end of day 14, cardiac tissue samples were histologically and biochemically examined. Results: In this experimental study, thiobarbituric acid reactive substances levels in the cardiac tissue were significantly higher in the CP group, whereas glutathione (GSH), superoxide dismutase (SOD), and CAT levels were significantly lower in this group. On the other hand, GSH and SOD levels in the CP + HP group were similar to the control group. There was no significant difference in cardiac CAT levels between Group CP and Group CP + HP. Conclusion: Hesperetin treatment leads to a decrease in oxidative stress, and associated histological damage. The findings of the current study suggest that HP has a protective effect against CP-induced cardiotoxicity.