Low extraction efficiency limits the availability and application of aescins, which exhibit various pharmacological activities. Here, we optimized parameters for ultrasound-assisted extraction of aescins from Aesculus chinensis seeds using deep eutectic solvent (DES)-water mixtures. Seven DES formulations were screened, and one providing the highest yield was selected for optimizing the molar ratio. The effects of four parameters were investigated using single-factor experiments combined with response surface methodology. The optimal extraction conditions were as follows: DES, a 1:1 mixture of 1,3-butanediol and lactic acid, with 42.5% water, used at a liquid-solid ratio of 25 mL/g; ultrasonic frequency, 40 kHz; extraction temperature, 70 °C; and extraction time, 27.5 min. The extraction yield under these conditions was significantly higher than that obtained via traditional methods. Aescin was purified from the DES extract using macroporous resin. AB-8 resin was most efficient in adsorbing aescin in static adsorption tests. Based on dynamic adsorption experiments, optimal separation, with a 100% recovery rate, was achieved by passing four bed volume (BV) of extract through AB-8 column, removing impurities with two BV of deionized water and four BV of 30% ethanol, and eluting with four BV of 60% ethanol at 5–10 mL/min. This green method should be suitable for large-scale applications.