Abstract: This study intends to explore the extraction process, physical and chemical properties, antioxidant and hypoglycemic activities of polysaccharides from wild bitter melon (WBM). Using the peel of fresh WBM fruit as raw material, based on the single factor experimental results, the liquid-to-material ratio, ultrasonic time and ultrasonic power in the ultrasound-assisted extraction (UAE) process were optimized by Box-Behnken response surface. Two polysaccharide components of WBP50 and WBP75 were obtained through UAE of the optimal conditions and gradient alcohol precipitation, and their physical and chemical properties, in vitro antioxidant and hypoglycemic abilities were evaluated. The results showed that: under the conditions of liquid-to-material ratio of 16 mL/g, ultrasonic time of 16 min, and ultrasonic power of 312 W, the actual yield of crude WBM polysaccharide (WBP) was 8.33%±0.13%. The total sugar, protein, total phenols, total flavonoids, and uronic acid contents of WBP50 and WBP75 were 76.73%/73.38%, 4.78%/0.35%, 0.36%/0.25%, 2.06%/0.86% and 72.85%/49.58%, respectively. The average molecular weights were 27.59 kDa and 23.20 kDa, respectively. WBPs were mainly composed of galacturonic acid, galactose, rhamnose, arabinose, and glucose. The DPPH, ABTS⁺ and hydroxyl radicals scavenging abilities of WBP50 and WBP75 were 11.28/11.40 μg Trolox/mg, 40.87/44.42 μg Trolox/mg, and 52.47/99.89 U/mg, respectively. Regarding hypoglycemic ability, both WBPs had certain α-amylase inhibitory ability and strong α-glucosidase inhibitory ability. The α-glucosidase inhibition rate of WBP50 and WBP75 reached 93.34%±1.11% and 79.04%±0.76% at a concentration of 750 μg/mL. The UAE of WBP has the advantages of time saving, convenience, high efficiency and low energy consumption, and the extracted WBPs have natural antioxidant and hypoglycemic functional activities. This study lays the foundation for future structural analysis and functional mechanism research of WBPs and provides theoretical references for developing hypoglycemic products and high-value utilization of WBPs.