Doxorubicin is widely applied in hematological and solid tumor treatment but limited by its off-target cardiotoxicity. Thus, cardioprotective potential and mechanism(s) of <italic>CVE</italic> in DOX-induced cardiotoxicity were investigated using cardiac and oxidative stress markers and histopathological endpoints. 50–400 mg/kg/day <italic>CVE</italic> in 5% DMSO in distilled water were investigated in Wistar rats intraperitoneally injected with 2.5 mg/kg DOX on alternate days for 14 days, using serum troponin I and LDH, complete lipid profile, cardiac tissue oxidative stress marker assays, and histopathological examination of DOX-treated cardiac tissue. Preliminary qualitative and quantitative assays of <italic>CVE</italic>’s secondary metabolites were also conducted. Phytochemical analyses revealed the presence of flavonoids (34.79 ± 0.37 mg/100 mg dry extract), alkaloids (36.73 ± 0.27 mg/100 mg dry extract), reducing sugars (07.78 ± 0.09 mg/100 mg dry extract), and cardiac glycosides (24.55 ± 0.12 mg/100 mg dry extract). 50–400 mg/kg/day <italic>CVE</italic> significantly attenuated increases in the serum LDH and troponin I levels. Similarly, the <italic>CVE</italic> dose unrelatedly decreased serum TG and VLDL-c levels without significant alterations in the serum TC, HDL-c, and LDL-c levels. Also, <italic>CVE</italic> profoundly attenuated alterations in the cardiac tissue oxidative stress markers’ activities while improving DOX-associated cardiac histological lesions that were possibly mediated via free radical scavenging and/or antioxidant mechanisms. Overall, <italic>CVE</italic> may play a significant therapeutic role in the management of DOX-induced cardiotoxicity in humans.