The enzymes of glucose and lipid metabolism are markedly altered in experimental diabetes. In the present study, we investigated the combined effect of tetrahydrocurcumin (THC) and gallic acid (GA), on hepatic key metabolic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Different combination doses of THC and GA (THC 40 and GA 10; THC 60 and GA 15 and THC 80 and GA 20 mg/kg body weight) were orally administered to diabetic rats for 45 days, after which activities of hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, sorbitol dehydrogenase in liver and glycogen content in liver and muscle were assayed. The activities of gluconeogeneic enzymes were found to significantly increase, whereas the activities of hexokinase, glucose-6-phosphate dehydrogenase and glycogen were found to significantly decrease in diabetic control rats. Combination drugs of THC and GA were able to restore the altered enzyme activities to almost near normal levels. Our results indicate that administration of THC and GA to diabetic animals normalizes blood glucose and causes marked improvement of altered carbohydrate metabolic enzymes during diabetes. In addition, oral administration of THC and GA combination to diabetic rats showed a decrease in the level of RBC count, PCV, MCV and MCH, while WBC count is typically increased (leukocytosis). THC and GA combination-treated rats showed a significant near to normal hematological parameters levels. These biochemical observations were supplemented by histopathological examination of pancreas section. The combination of THC and GA is more potent than the treatment with THC or GA alone.