Phenolic compounds are active compounds in Dendrobium formosum Roxb. ex Lindl. that have antidiabetic and anti-obesity activities. To obtain a high extraction yield of phenolic compounds from D. formosum, optimization of microwave-assisted extraction (MAE) was developed in this study using response surface methodology. The optimal conditions for phenolic compound yield were using absolute ethanol as the solvent, 540 W of microwave power, 49.37 s of extraction time, a 22.67 mL/g solvent-to-feed ratio, and three extraction cycles. The yields of coelonin, erianthridin, moscatilin, lusianthridin, gigantol and batatasin III when extracted under optimal conditions were 0.38 ± 0.04, 0.40 ± 0.05, 1.45 ± 0.18, 0.14 ± 0.01, 0.47 ± 0.05 and 0.58 ± 0.06 mg/g dry weight, respectively, with errors of less than 4% deviation from the predicted values. Our results indicate that MAE can obtain a higher yield of phenolic compounds and have a greater effect on glucose uptake than those of other extraction methods. Therefore, MAE has high efficiency for extracting phenolic compounds from D. Fomosum, yielding extracts with a high amount of compounds that exhibit antidiabetic activity.