Objective: Cisplatin (CDDP) has been known to be an effective antineoplastic drug; however, it has a cardiotoxic effect. Curcumin (CMN) andbeta-carotene (BC) have been suggested to protect biological systems against CDDP-induced damage. The current study was conducted toevaluate the possible protective roles of CMN and BC on CDDP-induced cardiotoxicity in rat cardiac tissues.Methods: A total of 49 adult female Wistar albino rats were equally divided into seven groups as follows: control (no medication), sesame oil (1mg/kg), CDDP (single dose injection two times as once a week, 5 mg/kg/week), BC (100 mg/kg), CDDP+BC (pretreated BC for 30 min before CDDPinjection), CMN (200 mg/kg), and CDDP+CMN (pretreated CMN for 30 min before CDDP injection). These treatments were applied intraperitoneallyfor CDDP and with gavage for CMN and BC. The oxidative/antioxidant indicators, inflammatory cytokines, and histopathological alterationswere examined.Results: These alterations included a marked increase in malondialdehyde (MDA) level, significant decrease in catalase (CAT) and superoxidedismutase (SOD) activities, and significant elevation of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interleukin (IL)-6 in the CDDP groupcompared with the other groups. Histopathologically, CDDP-induced severe myocardial degenerative changes were observed. However, theCDDP-induced disturbances in the above-mentioned parameters significantly improved by treatment with BC and particularly CMN.Conclusion: This study indicated that CDDP treatment markedly caused cardiotoxicity; however, treatment with CMN or BC ameliorated this cardiotoxicityin rats. Furthermore, these findings revealed that treatment with CMN has a higher cardioprotective effect than that with BC againstCDDP-induced cardiotoxicity in rat cardiac tissues.