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Ultrasound–microwave combined extraction (UMCE), gradient ethanol precipitation, chemical characterization, and antioxidant and hypoglycemic activities of <i>Lycium barbarum</i> leaf polysaccharides (LLP) were systematically studied. The optimal conditions for UMCE of LLP achieved by response surface method (RSM) were as follows: microwave time of 16 min, ultrasonic time of 20 min, particle size of 100 mesh, and ratio of liquid to solid of 55:1. Three novel polysaccharide fractions (LLP₃₀, LLP₅₀, LLP₇₀) with different molecular weights were obtained by gradient ethanol precipitation. Polysaccharide samples exhibited scavenging capacities against ABTS and DPPH radicals and inhibitory activities against α-glucosidase and α-amylase. Among the three fractions, LLP₃₀ possessed relatively high antioxidant and hypoglycemic activities in vitro, which showed a potential for becoming a nutraceutical or a phytopharmaceutical for prevention and treatment of hyperglycemia or diabetes.