Microwave extraction combined ultrasonic pretreatment of flavonoids from Periploca forrestii Schltr. was investigated in this study, extraction process was first performed in an ultrasoniccleaner, then treated by microwave irradiation. The optimum ultrasonic time of 25 min was selected by single-factor experiments. A response surface methodology has been used to obtain amathematical model that describes the process and analyzes the significant parameters ethanol concentration 59.92%, liquid to raw materials ratio 21.24 mL/g, microwave radiation time 209.53 s, and microwave power 274.14 w. In these optimum conditions, the yield of flavonoids from P. forrestii (TFPF) could be up to 9.11 +/- 0.08%, which was increased by 14.30 and 19.86% compared microwave extraction and ultrasonic extraction, respectively. In vitro suppresshyaluronidaseexperimentationshowed that TFPF purified using polyamide exhibited good anti-hyaluronidase ability with IC50 value of 1.033 mg/mL, possessing certain anti-antiallergic and potential applicationprospect in pharmaceutical production of treating inflammation and other related fields.