Abstract: The seed watermelon polysaccharide was extracted from seed watermelon using ultrasonic assisted extraction technique. The three factors:extraction time, extraction temperature and solid-liquid ratio were optimized based on response surface methodology ( RSM) . The results showed that the optimum seed watermelon polysaccharides extraction conditions was:ultrasonic treatment time 85min, extraction temperature 49℃, and solid/liquid ratio 1 ∶1.7g/mL, seed watermelon polysaccharides yield reached up to 4.128%. The molecular weight of seed watermelon polysaccharides was measured using SEC-HPLC and LLS:Mn=1.089×106g/moL. According to the scavenging capacity of seed watermelon polysaccharides against radicals, it showed that the scavenging capacity of seed watermelon polysaccharides agaist DPPH radicals was 68% at the concentration of 0.01⁰.32mg/mL, higher than VCsignificantly. The scavenging capacity of seed watermelon polysaccharides agaist hydroxyl radicals was 75.35% at the concentration of 5mg/mL and the scavenging capacity of superoxide radicals was 50% at the same concentration. The result showed that seed watermelon polysaccharides had strong free radical-scavenging capacity. And could be use as a potential natural antioxidant in the food and pharmaceutical industry.