Abstract An efficient method for the degradation of polysaccharides isolated from Sargassum fusiforme (PSF) was developed by using ascorbic acid in combination with H2O2. The degradation conditions were optimized using a Box-Behnken response surface design (BBRS). The optimum conditions were established as: concentration of ascorbic acid (VC) and H2O2 17.26 mM, degradation temperature 51 °C and degradation time 1.6 h. The DPPH radical scavenging rate of the degraded polysaccharides from S. fusiforme (DPSF) obtained under the optimal conditions was determined to be 75.22 ± 0.02%, which was well matched with the value (75.21%) predicted by the BBRS model. In vitro antioxidant activity of the polysaccharides was evaluated by determining their radical (hydroxyl radical, superoxide anion radical and DPPH radical) scavenging abilities, and ferric iron reducing power. The inhibitory activity on tyrosinase of DPSF was also evaluated. The results indicate that the degraded polysaccharide has superior antioxidant activity and anti-tyrosinase effect to those of the original polysaccharide.