Strawberry juice samples were sonicated at amplitude levels ranging from 40 to 100% at a constant frequency of 20 kHz for treatment times (2-10 min) and pulse durations of 5 s on and 5 s off. Sonication was found to reduce anthocyanin and ascorbic acid contents by 3.2 and 11%, respectively, at the maximum treatment conditions. Response surface methodology (RSM) based on a two-factor, five-level central composite design was employed to determine the effect of amplitude level and treatment time on anthocyanins (P3G), ascorbic acid (AA) content, and color values (L*, a*, and b*). The model predictions for the selected nutritional and quality parameters were closely correlated to the experimental results. RSM was demonstrated to be an effective technique to model the effect of sonication on strawberry juice quality while minimizing the number of experiments required.