Abstract: To study the optimal alkaline extraction technology of Sepia lycidas muscle polysaccharides， the extraction temperature，NaOH concentration and ratio of raw material to water were optimized by response surface methodology design based on single-factor tests. The optimal extraction conditions were extraction temperature of 90℃，NaOH concentration of 3%，and ratio of raw material to water of 1∶28 g/mL，respectively. Under these conditions，the extraction yield of polysaccharides was 0.68%. In addition，the antioxidant activity of polysaccharides was evaluated. When the concentration was 10 mg/mL，the scavenging rate of DPPH was 68% with the IC50 value of 7.62 mg/mL，and the scavenging ratio of·OH was 45.72% with the IC50 value of 12.44 mg/mL. The value of reducing capacity was 0.263. Moreover，IR spectroscopic analysis showed the extract had the common spectroscopic characteristics of polysaccharides.