Objective： The objective of this study was to screen out the active components with improved lipid metabolism in Grifola frondosa and to obtain the optimum extraction conditions. Method： Two kinds of in vitro screening methods， namely simulated bile micellar and lipase inhibition， were used to screen out the active components with stronger improving activity for lipid metabolism in Grifola frondosa. The extraction process of Grifola frondosa active components was optimized by single factor and response surface methodology. Result： The ethyl acetate extract （EAE） of Grifola frondosa had the strongest binding capacity of sodium deoxycholate and sodium cholate and inhibition of lipase activity. The best extraction conditions of the process were as follows： the ratio of solid to liquid was 1 ∶ 29（g/mL）， the ultrasonic time was 30 min and the extraction temperature was 50 ℃. The major components of EAE were identified by UPLC-MS/MS and found to be isocetin and cyanidin-3-O-rutinoside.