The main aim of this study was to evaluate the cytotoxic effects of chronic alcohol consumption on various regions of diabetic brain and preventive role of GTE. Clinical, experimental and histopathological observations indicate chronic, excessive alcohol consumption aggravates the free radical-mediated oxidative and nitrosative stress in several tissues including brain. Treatment with Epigallocatechin gallate (EGCG) significantly reduced the levels of oxidative/nitrosative stress paradigms, increased glutathione (GSH) levels and enhanced the activities of antioxidant enzymes. Histopathology evaluation revealed the possible influence of EGCG in reversing alcohol exacerbated diabetes-induced damage in cortex, cerebellum and hippocampus of brain. Furthermore, these studies have provided evidence to show how EGCG can exactly occupy the position in functional sites of nNOS (neuronal nitric oxide synthase) and induce a conformational change, inhibition of enzymatic activity and prevention of neurodegeneration/necrotic changes of tissue, in comparison with the rosiglitazone and glibenclamide. To summarise, this research has offered useful information on the action of EGCG that would provide potential protection against ethanol exacerbated diabetic brain damageand additional evidence for the use of EGCG as a lead compound for drug discovery.