Ultrasonic assisted-extraction technique was applied to extract the polysaccharide from Zagros oak (Quercus brantii Lindl). The effects of four independent factors (ultrasonic power (X1: 150-300 W), extraction temperature (X2: 50-90°C), extraction time (X3: 30-90 min), and the ratio of water to raw material (X4: 15-45)) on the extraction yield of polysaccharide from the leaves of Q. brantii Lindl (QBLP) were optimized using response surface methodology. The experimental data obtained were fitted to a second-order polynomial equation. The optimal extraction conditions for QBLP were determined as follows: X1: 205.8 W, X2: 81.9°C, X3: 55.6 min and X4: 23.4. Under these optimal conditions, the experimental yield was 19.42 ± 0.53%, which was well matched with the value predicted by the model 19.61%. The results indicated that polysaccharide has strong scavenging activities in vitro on DPPH and hydroxyl radicals. In addition, the QBLP showed good antimicrobial activity at 1.5-2.5mg/mL.