Water-extracted mycelial polysaccharide (WPS) from the endophytic fungus Fusarium oxysporum Dzf17 isolated from Dioscorea zingiberensis was found to be an efficient elicitor to enhance diosgenin accumulation in D. zingigerensis cultures, and also demonstrated antioxidant activity. In this study, response surface methodology (RSM) was employed to optimize the extraction process of WPS from F. oxysporum Dzf17 using Box-Behnken design (BBD). The ranges of the factors investigated were 1-3 h for extraction time (X-1), 80-100 degrees C for extraction temperature (X-2), and 20-40 (v/w) for ratio of water volume (mL) to raw material weight (g) (X-3). The experimental data obtained were fitted to a second-order polynomial equation using multiple regression analysis. Statistical analysis showed that the polynomial regression model was in good agreement with the experimental results with the determination coefficient (R-2) of 0.9978. By solving the regression equation and analyzing the response surface contour plots, the extraction parameters were optimized as 1.7 h for extraction time, 95 degrees C for extraction temperature, 39 (v/w) for ratio of water volume (mL) to raw material weight (g), and with 2 extractions. The maximum value (10.862%) of WPS yield was obtained when the WPS extraction process was conducted under the optimal conditions.