Diabetes mellitus (DM) is an important metabolic disease due to its worldwide increasing prevalence. Dendrobium nobile Lindl. is used in traditional Chinese medicine and has been reported to have antidiabetic activity. In this study, several extraction methods, including microwave-assisted extraction (MAE), were applied to D. nobile and the extracts were investigated for α-glucosidase inhibition potency. The optimal MAE conditions maximizing α-glucosidase inhibition were 540 W power, 60 sec extraction time, 40 mL/g solvent-to-feed ratio, and three extraction cycles. Our results show that MAE of D. nobile gave stronger inhibition of α-glucosidase with lower IC50 and faster extraction than the other extraction methods. IC50 of D. nobile extract was related to phenolic content with correlation -0.878, indicating that phenolics were the active compounds inhibiting αglucosidase in these plant extracts.