Ultrasonic-Assisted extraction (UAE) was applied for saponins extraction from Ophiopholis mirabilis and response surface methodology (RSM) was used to optimize the extraction technology. A first set of experiments were designed to optimize water bath temperature, ethanol concentration, the ratio of liquid to solid, ultrasonic time (min) and ultrasonic power (W) as the main variables affecting the extraction effect. A Box-Behnken design consisting of 15 experimental runs was then applied and a second-order polynomial model was used to explain the interactions between the main factors and the yield of saponins. The developed mathematical model was found to fit well with the experimental data and the optimized conditions were ultrasonic pretreatment time 30.9 min, ethanol concentration 64%, liquid /solid ratio 35:1, ultrasonic power 300W and water bath 70°C. Corresponding saponins content was 0.574%.