This study investigates the anti-diabetic effects of cyanidin-3-O-glucoside (C3G), an anthocyanin extracted from red bayberry, on insulin-resistant hepatocytes and diabetic db/db mice. The research demonstrates that C3G alleviates glucose metabolism disorders by enhancing insulin sensitivity in hepatocytes, increasing glucose consumption and glycogen synthesis in insulin-resistant cells. Western blot analysis showed that C3G inhibits the increase in PTP1B, a negative regulator of insulin signaling, and increases the phosphorylation of IRS-2, thereby improving insulin sensitivity. In vivo, C3G treatment in db/db mice significantly reduced blood glucose levels and improved glucose tolerance and insulin resistance. These findings suggest that C3G may offer a new approach for regulating glucose metabolism in type 2 diabetes mellitus (T2DM) through natural dietary bioactive components. The study also highlights the potential of anthocyanins in improving T2DM by targeting insulin resistance mechanisms. The results provide evidence that C3G can alleviate insulin resistance both in vitro and in vivo, offering a promising natural therapeutic option for T2DM.This study investigates the anti-diabetic effects of cyanidin-3-O-glucoside (C3G), an anthocyanin extracted from red bayberry, on insulin-resistant hepatocytes and diabetic db/db mice. The research demonstrates that C3G alleviates glucose metabolism disorders by enhancing insulin sensitivity in hepatocytes, increasing glucose consumption and glycogen synthesis in insulin-resistant cells. Western blot analysis showed that C3G inhibits the increase in PTP1B, a negative regulator of insulin signaling, and increases the phosphorylation of IRS-2, thereby improving insulin sensitivity. In vivo, C3G treatment in db/db mice significantly reduced blood glucose levels and improved glucose tolerance and insulin resistance. These findings suggest that C3G may offer a new approach for regulating glucose metabolism in type 2 diabetes mellitus (T2DM) through natural dietary bioactive components. The study also highlights the potential of anthocyanins in improving T2DM by targeting insulin resistance mechanisms. The results provide evidence that C3G can alleviate insulin resistance both in vitro and in vivo, offering a promising natural therapeutic option for T2DM.