Ethanol modified supercritical carbon dioxide (SC-CO2) extraction of flavonoids from Momordica charantia L. fruits and its antioxidant activity were performed. The influences of parameters such as temperature, extraction time and pressure on the yield of flavonoids were investigated. The antioxidant activities of flavonoids were assessed by means of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay and β-carotene bleaching test. The experimental data obtained indicated that pressure, temperature and time had significant effect on the extraction yield. The optimum extraction conditions, determined by the 3D response surface and contour plots derived from the mathematical models, were as follows: extraction temperature 46°C, pressure 33.4MPa, and extraction time 53.2min. Under these conditions, the experimental value was 15.47mg/g, which was well matched with value predicted by the model. The antioxidant activity of flavonoids obtained by ethanol modified SC-CO2 extraction method had higher antioxidant activity than the flavonoids extracted by conventional solvent extraction (CSE) method. The DPPH radical-scavenging ability of flavonoids obtained by ethanol modified SC-CO2 extraction method reached to 96.14±1.02%, equivalent to the clearance rate of ascorbic acid at 1.2mg/mL. Results indicated that ethanol modified SC-CO2 extraction was a suitable approach for the selective extraction of flavonoids from M. charantia L.