Cardiotoxicity is a major limiting factor for clinical use of doxorubicin (DOX) in chemotherapy. This study aimed to evaluate effectiveness of radish root extract (30mg/kg BW) to attenuate doxorubicin (DOX) - induced cardiotoxicity and to explore involved mechanisms. Phytochemical analysis of tested plant and assessment of antioxidant capacity against DPPH free radical were also performed. Treatment of male rats with DOX (2.5mg/kg BW, i.p.) twice weekly for 4 weeks elicited myocardial toxicity characterized by increased serum cTn-I, CK-MB, LDH and AST, decreased heart weight to body weight ratio, and myocardial degeneration. Other findings emphasized increased xanthine oxidase, lipid peroxidation, protein carbonyl, and nitric oxide, with diminished endogenous antioxidants in heart tissue, indicating provoked oxidative stress. Elevated serum inflammatory markers (TNF-α, CRP), adhesion molecules (VCAM-1, ICAM-1), fibrinogen and platelet activating factor, accompanied by marked thrombocytopenia were also validated. Results of radish analysis revealed strong scavenging activity against DPPH and presence of different polyphenols; flavonoids, tannins and alkaloids as a major phytoconstituents. Supplementation of radish extract has shown to be effective against toxic manifestations of DOX, most likely due to its radical scavenging and antioxidant activities. Therefore, radish extract can be suggested as a promising cardioprotective remedy for patients on DOX- based chemotherapy.