Abstract: In order to research the environment-friendly and high-efficiency extraction method of platycodin D and lobetyolin from the Platycodon radix, homogenate combined with ultrasonic-microwave synergistic extraction method were used for the first time to extract platycodin D and lobetyolin, and the contents were determined by high performance liquid chromatography（HPLC）. Based on the results of single factor experiments, taking ultrasonic-microwave time, microwave power and ethanol volume fraction as the key factors for optimization, and the contents of platycodin D and lobetyolin as the response value, the Box-Behnken response surface methodology was applied to optimize the optimal extraction process, which was compared with Soxhlet extraction and ultrasonic extraction process. The results showed that the best extraction parameters for platycodin D and lobetyolin were homogenate pretreatment for 3 min, ethanol volume fraction of 58%, material-to-liquid ratio of 1∶20 g/mL, microwave power of 580 W, extraction time of 15 min and temperature of 50 ℃, the predicted values of platycodin D and lobetyolin were 5.276 mg/g and 0.249 mg/g, and the measured values were（5.24±0.13） mg/g and（0.24±0.01） mg/g respectively, which were higher than the content of Soxhlet extraction（4.72 mg/g±0.24 mg/g; 0.20 mg/g±0.03 mg/g） and ultrasonic extraction（4.93 mg/g±0.15 mg/g; 0.21 mg/g±0.02 mg/g）. This research confirmed that homogenate combined with ultrasonic-microwave synergistic extraction method can efficiently extract the main active components in Platycodon radix, laying a theoretical foundation for the further development of Platycodon radix.