Doxorubicin (Dox) is a potent anthracycline chemotherapeutic agent. However, its efficacy is limited by its cardiotoxicity, which is driven by excessive oxidative stress, calcium overload, and mitochondrial dysfunction. These mechanisms ultimately result in cardiomyocyte death and cardiac dysfunction. Ivabradine, a hyperpolarization-activated cyclic nucleotide-gated channel blocker, has cardioprotective effects in heart failure and coronary artery disease. However, its potential for mitigating doxorubicin-induced cardiotoxicity (DIC) has not been explored. This study hypothesized that ivabradine reduces cardiac dysfunction in DIC by improving mitochondrial function, restoring calcium homeostasis, and attenuating apoptosis. For in vitro experiments, H9C2 cells were divided into four groups: control, ivabradine (3 μM), Dox (10 μM), and ivabradine co-treated with Dox, with treatments lasting 24 h. Cell viability and mitochondrial function were assessed. For in vivo experiments, male rats (n = 6 per group) were divided into control, ivabradine (10 mg/kg/day, p.o., 30 days), Dox (3 mg/kg, i.p., 6 doses), and ivabradine co-treated with Dox. Cardiac function, mitochondrial function, calcium regulatory proteins, and apoptosis were analyzed. Dox reduced cell viability, increased oxidative stress, and decreased ATP levels in vitro. Co-treatment with ivabradine increased cell viability and reduced oxidative stress but did not restore ATP levels. In rats, Dox impaired mitochondrial function, disrupted mitochondrial dynamics and mitophagy, and altered calcium homeostasis, resulting in cardiomyocyte apoptosis and left ventricular dysfunction. Ivabradine co-treatment attenuated these pathological changes and preserved cardiac function. These findings suggest the potential of ivabradine for cardioprotection against DIC.