A novel enzymatic extraction combined with response surface methodology was developed for polysaccharide extraction from marine algae. Box-Behnken design was employed to optimize concentration of enzyme, ratio of water to raw material and extraction time for high extraction yields. The optimal extraction conditions were as follows: a concentration of enzyme of 778.01 mg/g with ratio of water to raw material of 86.80 and extraction time of 129.93 min for Gelidium amansii and a concentration of enzyme of 997.03 mg/g with ratio of water to raw material of 98.76 and extraction time of 117.69 min for Laminaria japonica Aresch. Under the optimal conditions, extraction yields were 48.36% and 32.47%, respectively. Experimental data were fitted by multiple regression analysis to a secondorder polynomial equation and were statistically analyzed. The predicted model matched the experimental data well with coefficients of determination (R2) of 0.9864 and 0.9892, respectively.