Flavonoids were extracted from Odontonema strictum leaves by supercritical carbon dioxide, with ethanol. The effect of three independents variables (time, pressure and temperature) on the Total Flavonoid Content (TFC) were optimized by factorial investigation. The TFC and flavonoid recovery varies respectively from 99.33 to 247.78 mg/g of dried extract and 10.68-18.92 mg/g of dried leaves powder, while the conventional solvent extraction (CSE) yielded 36.45 mg/g and 3.13 mg/g. Analysis of the factorial identified the optimal conditions with an extraction time of 270 min and a pressure of 200 bar, the temperature had no effect within the tested ranges. The predicted TFC was 203.11 mg/g under optimal conditions and experimentally 230.48 mg/g. The antioxidant activity with 2,2-Diphenyl-1-picrylhydrazyl method of the extracts under optimum conditions was 49.21% while the CSE extract was 37.05%. The TLC analysis of the supercritical fluid extracts from the optimum conditions showed 5 majors flavonoids.