The orthogonal design was used to optimize enzyme-based ultrasonic/microwave-assisted extraction (EUMAE) of orcinol glucoside (OG)-enriched extract from the rhizomes of Curculigo orchioides Gaertn. (RCO). The results indicated that the highest extraction yield of OG by EUMAE could reach 92.13 % using 70 % ethanol as solvent under the optimal conditions (the ratio of raw material to solvent was 1:8, extraction time was 15 min, extraction temperature was 50 °C, amount of enzyme was 3 mL, and microwave irradiation power was 400 W), which was more efficient than that by the conventional and classical extraction methods. Finally, the crude extract was then purified by macroporous adsorption resin, the OG content in the purified extract increased to 91.70 %. Compared to the conventional and classical methods, EUMAE was superior in terms of higher yields, less energy consumption, and better selectivity of the extracts controlled by the extraction parameters. Furthermore, it was obvious that OG from RCO had significant effect on the antioxidant activity.