Abstract: White lentils, broad beans, peas and buckwheat were used as raw materials, supplemented with wolfberries, which was a plant of the same origin as food and medicine, to prepare a new instant wolfberry grain blending powder with low glycemic index (GI), and its optimal formulation and hypoglycemic effect in mice with type 2 diabetes were investigated in the study. The formulation of the wolfberry grain blending powder was optimized by using the sensory score as an index, single factor experiments, Plackett-Burman experiments, steepest ascent experiments and Box-Behnken experiments were used to optimize the blending powder formula. A type 2 diabetes mouse model was established to evaluate the hypoglycemic effect of the blending powder. The results showed that the optimal compounding ratios of wolfberry grain blending powder were as follows: wolfberry powder 23%, white lentil powder 23%, buckwheat powder 20%, broad bean powder 17% and pea powder 17%, the corresponding amounts: 14.0 g for wolfberry powder, 14.0 g for white lentil powder, 12.0 g for buckwheat powder, 10.0 g each for broad bean and pea powders. In animal experiments, compared with the model group, fasting blood glucose level, organ index, activities of alanine transferase (ALT) and aspartate aminotransferase (AST), and the levels inflammatory factors, triglyceride (TG) and total cholesterol (TC) were significantly decreased (P<0.05) in the mice treated with the grain powder. The body weight, activity of superoxide dismutase (SOD) of the mice were significantly increased (P<0.05). The pathology of the liver, kidneys and pancreas of type 2 diabetic mice was effectively alleviated by the new wolfberry grain blending powder.