Green and efficient extraction of natural products from biomass is considered an important field in the pharmaceutical and biochemical industries. Recently, deep eutectic solvents (DESs) have been growing in interest as sustainable and safe solvents. In this study, we aimed to provide a practical example using a popular traditional Chinese medicine, Flos sophorae, showcasing the tuneability of DESs as designer solvents to selectively and efficiently extract bioactive compounds from biomass. As a result, a solvent called PG-1 that was tailor-made from a 2:5 mixture of L-proline and glycerol using freeze-drying method, was more effective than methanol for extraction of quercetin, kaempferol, and isorhamnetin glycosides from Flos sophorae. With PG-1-based ultrasound-assisted extraction (UAE), operational conditions including the DES content in the extractant, extractant-to-sample solid ratio, and ultrasound irradiation time for UAE were statistically optimized using a central composite design combined with response surface methodology. The resulting extraction method in which 50 mg of sample powder was extracted by UAE for 45 min using 1.00 mL of aqueous solution containing 90% w/w PG-1 was found to be a greener and more efficient process than common extraction methods such as methanol-based UAE and heat reflux extraction that are generally environmentally harmful. Based on the antioxidant activity measured by DPPH assay, the tailor-made extractant exhibited additive activity arising from its component, L-proline. Recovery of extracted flavonoids from the DES, which was assessed from rutin, since it is the major flavonoid extracted, was 75% with the use of water as an anti-solvent, and could reach as high as 92% with the simple application of C18 solid phase extraction (SPE). In comparison, the recovery efficiency of the anti-solvent method was significantly reduced for the flavonoid glycosides from the real Flos sophorae extracts, while the efficiency of the SPE method was reasonably high (81-87%). The present study suggests that DESs are truly designer solvents that can be used as sustainable and safe extraction media for pharmaceutical and biochemical applications.