Prosopis farcta (Banks et Sol.) Eig., is a widely distributed plant, that is rich in health benefits components. This study aims to optimize the ultrasonic-assisted extraction parameters of P. farcta leaves in order to maximize total phenolic content (TPC), total flavonoid content (TFC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, using response surface methodology (RSM). A Box-Behnken design (BBD) with three levels and three variables was employed, the independent variables were extraction temperature (20, 40 and 60°C), extraction time (20, 40 and 60 minutes) and ethanol concentration (20, 45 and 70%). Results show that all three extraction parameters have great effects on the TPC, TFC, and DPPH scavenging values, the optimal conditions were (extraction temperature: 53.93°C, extraction time: 51.11 minutes and ethanol concentration: 65.45%), under these conditions, the experimental results were (TPC: 109.89 mg GAE/g DW, TFC: 11.287 mg RE/g DW and DPPH: 37.503%), these results are matching well with the theoretical predicted values which proves that RSM models were accurate and reliable. Strong correlations were found between TPC, TFC, and DPPH scavenging activity. This study revealed the importance of P. farcta as a natural source of antioxidants, and highlighted the optimal extraction conditions that can be effectively employed for maximizing production of natural antioxidants from P. farcta leaves.