Response surface methodology (RSM) was applied to optimize the solvent extraction process of pharmaceutically active flavonoid glycosides from Ginkgo biloba L. The three most critical experimental parameters (solvent ethanol content, particle size of the powdered Ginkgo biloba L.fragments and the extraction time) were selected in accordance with Plackett-Burman screening design. A mathematical model has been adapted using the RSM coupled with face-centered central composite design (FCCCD) to predict the change in extraction yield of flavonoid components. The regression analysis results indicated the optimal values for reaching the maximum extraction yield of flavonoids from Ginkgo biloba L. were 68.22 %, 154.09 m, and 150.33 minutes for the ethanol content, particle size and extraction time, respectively.