In this study, 10 different natural surfactants were compared as additives for the simultaneous extraction of lipophilic regaloside A and water-soluble polysaccharides from tiger lily ( Lilium lancifolium Thunb.) bulbs by homogenate-ultrasound-synergistic extraction. Four significant factors that affect the yields of regaloside A and polysaccharides, including homogenate speed, ultrasound irradiation power, reaction temperature and ultrasound irradiation time, were screened by single-factor experiments and Plackett-Burman design and then optimized using Doehlert matrix design combined with a desirability function. The optimal extraction process conditions were obtained as follows: APG06 ( n -hexyl glucoside) surfactant concentration of 0.6%, homogenate speed of 20000 r/min, homogenate time of 6 min, liquid solid ratio of 20 mL/g, ultrasound irradiation power of 300 W, ultrasound irradiation time of 52 min, reaction temperature of 62.8 °C, and buffer and cavitation times of 1.5 s and 2.0 s, respectively. Under the optimal extraction conditions, regaloside A and polysaccharides yields of 2.797 ± 0.084 mg/g and 0.493 ± 0.016 g/g are obtained with relative standard deviations of 3.00% and 3.50%, respectively. The results of the method validation and comparison with the conventional method show that homogenate-ultrasound-synergistic extraction with APG06 as an additive is a green, efficient and energy-saving extraction method. Compared with the traditional extraction method, HUSE with APG06 as an additive is an effective method to extract regaloside A and polysaccharides from L. lancifolium bulbs. This study provides a reference for the development of green low carbon natural product extraction process. • Use homogenate-ultrasound-synergistic extraction of regaloside A and polysaccharides. • Alkyl polyglucoside was first added to extract phenolic acid glycerides (regaloside A). • 0.6% n -hexyl glucoside was chosen as the extraction additive. • Use combination of Plackett-Burman design and Doehlert matrix design. • Alkyl polyglucoside has obvious advantages on yield and safety compared with ethanol.