The study was designed to evaluate the cardiotoxicity of Doxorubicin in Wistar rats and amelioration by ascorbic acid and spirulina. Female rats were divided into four groups. Animals were slaughtered at the end of the experiments (28th day) and collected blood for analysis. The biochemical assays showed significant (P<0.05) increase in creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), cardiac troponins (cTn) in Doxorubicin treated rats. There was considerable amelioration in ascorbic acid and spirulina groups. Grossly, heart revealed severe congestion, endocardial haemorrhages. Histopathological changes in heart of doxorubicin group revealed severe disruption, separation, degeneration, necrosis, fragmentation of muscle fibers with endocardial haemorrhages, edema, and focal infiltration of lymphocytes. The ameliorative groups 3 and 4 showed mild to moderate improvement. The tissue enzymes assays revealed a significant (P<0.05) increase in TBARS and significant (P<0.05) decrease of GSH and SOD activities in group 2. The ameliorative groups 3 and 4 showed mild to moderate improvement.