Abstract Response surface methodology (RSM) was applied to optimize the extraction of crude polysaccharides from Opuntia dillenii (Ker–Gaw) Haw. A three-level, four-variable Box–Behnken design was employed to obtain the best possible combination of extraction temperature (80–90°C), extraction time (50–70min), number of extraction cycle (1–3 times), and ratio of water to raw material (8:1–12:1, v/w) for maximum yield of crude polysaccharide. Besides, the antioxidant capacity of crude polysaccharide was evaluated by DPPH assay. The results showed that optimized extraction conditions were extraction temperature 85°C, extraction time 63.7min, extraction 2 times and ratio of water to raw material 11.14:1. Under these conditions, the experimental yield was 27.36±0.21%, which is well in close agreement with the value (27.44%) predicted by RSM model. Pharmacological test showed that O. dillenii crude polysaccharides had a good antioxidant activity.