This study describes an enhanced technique for extracting platycodin D and lobetyolin from the roots of Platycodon grandiflorus using an ultrasound-assisted approach with polyethylene glycol (PEG) as an additive. The optimization conditions were obtained by combining single-factor and Box Behnken design experiments and included the following results: The extraction solvent was 10% polyethylene glycol (PEG200-PEG400, 1:1), the liquid-to-material ratio was 24 mL/g, the ultrasonic irradiation power was 288 W, the ultrasonic irradiation time was 44 min, the reaction temperature was 30 °C, the cavitation time was 1.5, and the buffer time was 1.5 s. Under these conditions, the yield of platycodin D was 5.22 ± 0.13 mg/g, and the yield of lobetyolin was 0.15 ± 0.01 mg/g. The total yield of platycodin D and lobetyolin were significantly higher than those obtained with ethanol solution as the extraction solvent. In summary, the ultrasound-assisted method in conjunction with response surface experimental design is a quick and effective sample extraction technique for platycodin D and lobetyolin that can also be used to extract substances from other plants. • Use ultrasonic-assisted extraction of platycodin D & lobetyolin from P. grandiflorus. • Polyethylene glycol was first added to extract triterpenoid and alkynyl glycosides. • 10% PEG200-PEG400 (1:1, v/v) was chosen as the extraction solvent. • Determine optimum conditions of platycodin D & lobetyolin by response surface method. • Compared with ethanol as solvent, PEG has obvious advantages in terms of yield and safety. [ABSTRACT FROM AUTHOR]