It has been reported that enzymatic digestion of algae could improve the yield and enhance the biological activity compared to water and organic extraction. Our previous research indicated that Celluclast-assisted extract of (SF) possessed higher carbohydrate content and stronger antioxidant activity compared to water and other enzyme-assisted extracts. In the present study, we evaluated the antioxidant activities of polysaccharides from SF (SFPS) in vitro in Vero cells and in vivo in zebrafish. SFPS was obtained by Celluclast-assisted hydrolysis and ethanol precipitation. Results showed that SFPS contained 74.55 ± 1.26% sulfated polysaccharides and effectively scavenged 1, 1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and alkyl radicals. SFPS significantly and dose-dependently scavenged intracellular reactive oxygen species (ROS) and improved cell viability. Further studies indicated that SFPS reduced apoptotic body formation through downregulation of proapoptotic protein (Bax and cleaved caspase-3) levels and upregulation of antiapoptotic protein (Bcl-xL and PARP) levels in 2,2-azobis(2-amidinopropane) hydrochloride (AAPH)-treated Vero cells. In addition, SFPS showed strong protective effect against AAPH-stimulated oxidative stress in vivo in zebrafish, as demonstrated by the improved survival rate, reduced heart rate, and decrease in ROS, cell death, and lipid peroxidation levels. These results suggest that SFPS possesses strong in vitro and in vivo antioxidant activity and can be a potential ingredient in the pharmaceutical and cosmeceutical industries.