Response surface methodology(RSM) was used for optimizing ultrasound-assisted extraction of malania polysaccharides. Based on single-factor experiments, three independent variables, namely extraction time(A), ultrasonic temperature(B), and material/water ratio(C), were selected as casual factors. The experiments were arranged according to Box-Behnken central composite experiment design. Response surface methodology was applied to determine the effect of central composite experiment design and casual factors on the yield of malania polysaccharides(Y) which were determined by the phenol-sulfuric acid method. In this foundation, Design Expert software was employed and a second order quadratic equation for malania polysaccharides extraction was established: Y=4.29+0.16A+0.18B+0.39C−0.080AB+0.072AC+0.23BC−0.45A2+0.21B2−0.15C2. It showed that the factors of affecting the extraction rate of malania polysaccharides in order were as fo1lows: material/water ratio(C)>ultrasonic temperature(B)> extraction time(A). The model equation was very significant (P<0.0001), and adjustment R2 was 0.9792. It demonstrated that the degree of model fitting was well. By analyzing the response surface plots and their corresponding contour plots as well as solving the quadratic equation, the optimal values of the variables were as follows: extraction time 45 min, ultrasonic temperature 36.67 °C, and material/water ratio 1∶25 (g/mL). Under such conditions, the predicted best extraction yield of malania polysaccharides was 5.17%, which was very consistent with the experimental value (5.02%) with a relative error of 2.90%. The applicability of the model equation for predicting the optimum response values was verified effectively by the validation data. Antioxidant biological activity of malania polysaccharides was studied under two different situations. The result showed that the inhibition rates of malania polysaccharides separated by ceramic membrane microfiltration and alcohol sedimentation on hydroxyl free radical and DPPH free radical were increased significantly within the range of certain concentrations. The highest hydroxyl free radical and DPPH free radical scavenging activity (73.18% and 77.59%) were found with 4.57 mg/mL and 2.44 mg/mL, respectively. It indicated that malania polysaccharides could be as new, safe, effective and natural antioxidants.