This study focuses on the optimization of ultrasound-assisted extraction (UAE) of total flavonoids from Uvaria chamae root bark. As optimisation method, Response Surface Methodology (RSM) was used to investigate the effect of independent variables on the ultrasound-assisted extraction (UAE) process. The factors highlighted during the UAE were temperature (°C) X1, sonication time (s) X2, and solid to liquid ratio (mL.mg-1) X3; extraction yield being the expected response. The maximum extraction ef?ciency was achieved with the optimal UAE condition at 55 °C, 20 min and 40:1 mL.mg-1. At those optimal conditions, extraction yield of 16.34 % and the total flavonoids of (178.624±2.512) µg EQ/g of extract were obtained. Regarding to antioxidant assessment, the DPPH (2, 2-diphenyl-1-picrylhydrazyl) method was used. It emerges from this evaluation that the UAE extract exhibited the highest values of DPPH radical-scavenging assay with inhibition concentration (IC50) value of (0.075±0.001) mg/mL better than BHT taking as control with and IC50 value of (0.089± 0.022) mg/mL and compared to CSE. The experimental and predicted values were in good agreement, which suggested that UAE is more ef?cient compared to conventional solvent extraction and can be used to obtain an extract with maximum extraction yield and improved active ingredients.