Abstract: Objective: The aim of this work was to explore the hypoglycemic effect of Enteromorpha prolifera polyphenols (EPP) on type 2 diabetic mice, and to provide theoretical basis for the development of EPP products. Methods: EPP crude was extracted from Enteromorpha prolifera by ethanol solution extraction, and purified by silica gel column chromatography. The model of type 2 diabetes in mice was established by alloxan. The experimental mice were divided into blank control group, model control group, EPP low dose group (EPP-L), EPP midium dose group (EPP-M), EPP high dose group (EPP-H), and positive control group. The basic indicators of mice, as well as lipid metabolism and serum antioxidant indicators, were measured by continuous gastric perfusion for 4 weeks. Results: At the 4th week of the experiment, the averaged weight of mice in EPP-H group reached 32.16±1.97 g, which was not significantly different from that of the positive control group (P>0.05). The fasting blood glucose concentration of EPP-H group was 11.78±1.62 mmol/L, and there was no significant difference between EPP-H group and the positive control group (P>0.05). EPP-H clearly had significantly improved both the glucose tolerance (P<0.05) and the abnormal glucose tolerance of mice. The concentrations of superoxide dismutase, catalase, glutathione peroxidase, high-density lipoprotein cholesterol, and serum insulin levels in EPP-H mice were 157.36±6.71 U/mg, 168.07±1.77 U/mg, 378.14±9.74 U/mg, 1.31±0.04 mmol/L, and 19.03±2.01 mU/L, respectively, compared with the model control group, it was significantly increased (P<0.01), and the contents of malondialdehyde, triglyceride, total cholesterol and low-density lipoprotein cholesterol were significantly decreased (P<0.05). Conclusion: Polyphenols from Enteromorpha prolifera can effectively improve the basal metabolism of type 2 diabetic mice and repair the peroxide damage of diabetic mice, and may play a role in lowering blood sugar.