In order to enhance the nutritive value and functional activity of quinoa, response surface methodology was employed to optimize the fermentation technology based on the single factor experiment to increase the total phenols. Moreover, the antioxidant and α-glucosidase inhibiting activity of quinoa were compared. The results showed that the optimal fermentation conditions were as follow: yeast 1.7%, fermentation time 80 h, moisture content 16 mL, and the average content of total phenols from fermented quinoa was reached to (5.31±0.11) mg/g under these conditions, which was close to the predicted value with the relative error is only 1.12%. Moreover, compared to unfermented quinoa, the fermentation treatments could obviously increase the content of total phenols, especially quercetin and vanillic acid, which reached to (113.4±8.73) mg/kg and (44.7±2.54) mg/kg, respectively. The activity assay indicated that the scavenging activity against DPPH and ABTS free radicals of the fermented quinoa were remarkably increased, with the IC₅₀ were 16.42 mg/mL and 1.51 mg/mL, respectively. Meanwhile, the α-glucosidase inhibiting activity was averagely increased 12.41%. Therefore, the fermented treatment of quinoa could obviously increase the content of total phenols, and enhance its nutritive value and biological activity.