The extraction of flavonoids from Osmanthus fragrans residues was optimized using ultrasonic device. The reaction parameters studied were the ethanol concentration (60-100%), the extraction time (1.5-2.5 h) and temperature (70-90°C) using response surface methodology based on Box-Behnken design. A mathematical model was developed to show the effects of each variable and their combinatorial interactions on extraction yield of flavonoids. A high coefficient of determination (R^2 = 99.57%) indicated good agreement between the experimental and predicted values of extraction yield. The optimal values of the variables were as the followings: ethanol concentration, 82%; extraction time, 2.1 h; and temperature 82°C. The ultrasound-assisted extractions supported higher extraction yields as compared to traditional extraction and could be recommended as an alternative method for extraction of flavonoids compounds from O. fragrans residue.