This study was designed to investigate the possible mechanisms whereby Curcuma longa could protect against cardiotoxicity induced by doxorubicin. Administration of doxorubicin (15 mg/kg i.p.) induced cardiomyopathy manifested by significant elevation in serum creatine kinase MB (Ck-MB) and lactate dehydrogenase (LDH) activities. In addition, cardiotoxicity was further confirmed by significant increase in each of serum and cardiac malondialdehyde (MDA) level, serum iron and nitric oxide concentrations, cardiac calcium level, catalase and glucose-6 phosphate dehydrogenase activities as well as by the noticeable reduction in cardiac total antioxidant capacity, vitamin C levels and blood glutathione (GSH) concentration. Oral administration of Curcuma longa ethanolic or water extract (200 mg/kg) prior to doxorubicin produced a significant protection which was evidenced by significant reduction in mortality, CK-MB and LDH -activities. Moreover, they significantly increased GSH markedly, decreased cardiac calcium, and cardiac and serum MDA. In addition, both extracts significantly reduced serum nitric oxide, increased cardiac ascorbic acid, and ameliorated the antioxidant enzymes activities. In conclusion, Curcuma longa extracts renders resiliency against doxorubicin cardiotoxicity due to their contents of polyphenolic compounds that might serve as novel adjuvant therapy with doxorubicin.