In this study the phenolic compounds piceid, resveratrol and emodin were extracted from P. cuspidatum roots using ultrasound-assisted extraction. Multiple response surface methodology was used to optimize the extraction conditions of these phenolic compounds. A three-factor and three-level Box-Behnken experimental design was employed to evaluate the effects of the operation parameters, including extraction temperature (30–70 °C), ethanol concentration (40%–80%), and ultrasonic power (90–150 W), on the extraction yields of piceid, resveratrol, and emodin. The statistical models built from multiple response surface methodology were developed for the estimation of the extraction yields of multi-phenolic components. Based on the model, the extraction yields of piceid, resveratrol, and emodin can be improved by controlling the extraction parameters. Under the optimum conditions, the extraction yields of piceid, resveratrol and emodin were 10.77 mg/g, 3.82 mg/g and 11.72 mg/g, respectively.