Numerous clinical and bioavailability studies addressed epigallocatechin gallate (EGCG) beneficial effects; however, our previous work revealed EGCG-induced nephrotoxicity in the presence of diabetes. In this study, the potential myocardial toxicity of EGCG preparation (100 mg/kg/day, IP; 4 days) in diabetic mice injected with streptozotocin (STZ; 150 mg/kg, IP) was investigated. Diabetic mice receiving EGCG preparation showed electrocardiographic changes in addition to elevation of both serum creatine kinase-MB and troponin-I levels accompanied by microscopic myocardial damage. Additionally, myocardial NADPH oxidase, lipid peroxides and nitrotyrosine were increased in the vicinity of decreases of nuclear factor erythroid 2-related factor 2, hemeoxygenase-1, reduced glutathione, total antioxidant capacity, glutathione peroxidase and reductase and heat shock protein 90. Moreover, in diabetic mice, EGCG preparation increased myocardial nuclear factor-kappa B and tumor necrosis factor-alpha in addition to pronounced overexpression of inducible nitric oxide synthase and active caspase-3. Therefore, this study substantiates that EGCG-mediated deterioration compromises diabetes-induced cardiotoxicity to solidify our previous report for its potential nephrotoxicity in the same experimental setting.