Abstract: The aim of this research was to optimize the polysaccharides extraction process from the peels of Akebia trifoliate, and evaluate its in vitro antioxidant and hypoglycemic activity. The ultrasonic-assisted extraction process of polysaccharides from the peels of Akebia trifoliate was optimized using single-factor combined with orthogonal experiment. The antioxidant activity of polysaccharides from the peels of Akebia trifoliate was investigated by using DPPH radical scavenging rate and total reducing ability as the indicators. The hypoglycemic activity of polysaccharides from the peels of Akebia trifoliate was explored using α-glucosidase and α-amylase inhibition rate as the indicators. The results demonstrated that the optimal ultrasonic-assisted extraction process of polysaccharides from the peels of Akebia trifoliate was ultrasound power 280 W, ultrasound time 60 min, extraction temperature 50 ℃, solid-liquid ratio 1:40 g/mL, respectively. Under the optimal process condition, the extraction rate of polysaccharides from the peels of Akebia trifoliate was 5.91%±0.20%. Within the measured concentration range, polysaccharides from the peels of Akebia trifoliate had the preferable DPPH radical scavenging and reducing ability. In addition, the IC₅₀ values of polysaccharides from the peels of Akebia trifoliate and V_C for scavenging DPPH free radicals were 0.329 and 0.077 mg/mL, separately. The IC₅₀ values of polysaccharides from the peels of Akebia trifoliate for inhibiting α-glucosidase and α-amylase activity were 0.386 and 0.307 mg/mL, respectively. This research proved that the polysaccharides from the peels of Akebia trifoliate extracted by this optimal process had better in vitro antioxidant and hypoglycemic activity.