In this study, quartz sand with particularly sharp nanoscale edges acted like a nanoscale knife physically cut cells of Polygonatum cyrtonema Hua into nanosized particles and was synergized with natural deep eutectic solvent to extract steroidal saponins of Polygonatum cyrtonema Hua. The natural deep eutectic solvent (choline chloride-lactic acid)-synergistic quartz sand-assisted extraction was optimized using response surface methodology. The steroidal saponins purified with AB-8 macroporous resin were identified using ultra-high-performance liquid chromatography-triple time of flight mass spectrometry. The results showed that the experimental total saponins content value (36.97 ± 0.12 mg dioscin equivalent/g dry weight) at optimal extraction conditions with a temperature of 68°C, a rotational speed of 20 400 rpm, shear time of 4.3 min, the liquid-solid ratio of 38 ml/g, was close to the maximum possible theoretical value (36.64 mg dioscin equivalent/g dry weight). A total of 20 steroidal saponins were identified, among which the content of (25R)-Kingianoside E was the highest (102.66 ± 3.47 mg/g). Furthermore, a new steroid saponin (3β,25S)-26-(β-D-glucopyranosyloxy)-22-hydroxyfurost-5-en-3-yl 4-O-β-D-glucopyranosyl-β-D-galactopyranoside+Glc was found for the first time. These results revealed that natural deep eutectic solvent-synergistic quartz sand-assisted extraction was an efficient and green method to extract a variety of steroidal saponins.