Abstract: The optimal extraction of polysaccharides from Sepia pharaonis viscera was studied using Box-Behnken design, and the antioxidant activities, the moisture-absorption and moisture-retention properties of the polysaccharides were also investigated. The optimal extraction conditions were as follows:NaCl concentration was 2.9%, ratio of water to raw material was 30 mL/g, extraction time was 1.8 h and extraction temperature was 80℃. Under the optimal conditions, the yield of polysaccharides was 1.08%. The results of FTIR spectra indicated the polysaccharides was pyranoid glucan with α-glycosidic bond. The polysaccharides was capable of scavenging·OH, DPPH·and ABTS free radicals in a concentration dependent manner in vitro, especially in scavenging ABTS radical, the scavenging ratio reached almost 80% when the concentration was 1.0 mg/mL. Furthermore, the polysaccharides had certain moisture-absorption and moisture-retention abilities as compared to PEG-6000, glycerol and chitosan. These results indicated that the polysaccharides could be of potential utility in food, pharmaceutical and cosmetic industries as a type of effective natural antioxidant and moisturize.