In this study, a T2DM model was established in ICR mice through the administration of a high-sugar and high-fat diet combined with the intraperitoneal injection of streptozotocin to explore the hypoglycemic effect of polysaccharides from Physalis alkekengi L. After six weeks of treatment, the mice in the high-dosage group (800 mg/kg bw) displayed significant improvements in terms of fasting blood glucose concentration, glucose tolerance, serum insulin level, insulin resistance, and weight loss (p < 0.05). Here, INS is linked to type 2 diabetes mellitus.