The Box-Behnken design was used to investigate the effect of three independent variables – time, temperature and solvent-to-solid ratio on the responses of total phenolics, total flavonoids, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and cupric ion reducing antioxidant capacity (CUPRAC) of date fruit methanolic extracts. Response surface analysis showed that the optimal ultrasound extraction parameters that maximized the responses were 30 min, 298 K and 74.4 ml/g. Under optimum conditions, UHPLC-DAD-MS/MS was used to tentatively characterize 11 phenolic compounds. The experimental values for the quantification of phenolic compounds and antioxidant activities are in accordance with the predicted values, indicating the suitability of the model and the success of response surface methodology in optimizing the ultrasound extraction conditions.