© 2019 Wiley Periodicals, Inc. Maize silks have been used in Mexico for centuries as a natural-based treatment for various illnesses, including obesity and diabetes. It has been shown in mice that intake of maize silk extracts reduces the levels of blood glucose. However, it is not clear how or what maize silk compounds are involved in such an effect. A hypothesized mechanism is that some maize silk compounds can inhibit carbohydrate hydrolyzing enzymes like α-glucosidases. This work aimed to assess the capability of both saccharides and phenolic compounds from maize silks to inhibit intestinal α-glucosidases. Results showed that saccharides from maize silks did not produce inhibition on intestinal α-glucosidases, but phenolics did. Maize silk phenolics increased the value of Km significantly and decreased the Vmax slightly, indicating a mixed inhibition of α-glucosidases. According to the molecular docking analysis, the phenolics maysin, methoxymaysin, and apimaysin, which had the highest predicted binding energies, could be responsible for the inhibition of α-glucosidases. Practical applications: The International Diabetes Federation (IDF) reported in 2017 that diabetes affects over 424 million people worldwide, and caused 4 million deaths. Non-insulin-dependent diabetes or type 2 diabetes mellitus (T2DM) accounts for ∼90% of cases. T2DM is characterized by insulin resistance and pancreatic β-cell failure. Therapy for T2DM includes the use of sulfonylureas, thiazolidinediones, biguanides, and α-glucosidase inhibitors. Regarding the α-glucosidase inhibitors, only few are commercially available, and these have been associated with severe gastrointestinal side effects. This work aimed to assess the capability of both saccharides and phenolic compounds from maize silks to inhibit intestinal α-glucosidases. Results from this work evidenced that maize silk polyphenols acted as effective inhibitors of intestinal rat α-glucosidases. Computational analysis of maize silk polyphenols indicated that maysin, a particular flavonoid from maize silks, could be responsible for the inhibition of α-glucosidases.