The current work aims to optimize the ultrasound-assisted extraction (UAE) of Cistus salviifolius L. (aerial parts) antioxidative phenolic compounds using response surface methodology. A Box-Behnken design has been conducted to investigate the effect of four factors, namely: (i) percentage of ethanol (50-90%, v/v), (ii) temperature (40-80°C), (iii) solvent-solid ratio (10-50 mL g-1) and (iv) extraction time (5-25min) on four responses, namely: total phenolic content (TPC), total flavonoid content (TFC) 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical inhibition, and ferric reducing antioxidant power (FRAP). Based on the desirability index, UAE with 50% (v/v) ethanol, at 80 oC, using a solvent-solid ratio of 32.24 mL g-1, for 21 min resulted in the maximum recovery of phenolic antioxidants. Under optimum conditions, the experimental values of TPC, TFC, % DPPH scavenging activity, and FRAP were 171.67 ± 4.69 mg GAE g-1, 26.87 ± 0.78 mg CE g-1, 81.31 ± 0.16%, and 1038.22 ± 7.69 μmol TE g-1, respectively. Results highlight that the developed eco-friendly method is appropriate for the improved recovery of phenolic antioxidants from C. salviifolius L.