| Summary: | <i>Englerophytum magalismontanum</i>, a medicinal plant with ethnopharmacology use, has a dearth of information regarding its antidiabetic properties. This study evaluated the crude methanol leaf extract of <i>E. magalismontanum</i> and its fractions for total phenolic content, antioxidant activity, and digestive enzymes (α-amylase and α-glucosidase) inhibitory activity using standard methods. The total phenolic content (56.53 ± 1.94 mg GAE/g dry extract) and DPPH Trolox antioxidant equivalent (TAE) (1.51 ± 0.66 µg/mL) of the methanol fraction were the highest among the fractions. The IC<sub>50</sub> values of the methanol fraction against α-amylase (10.76 ± 1.33 µg/mL) and α-glucosidase (12.25 ± 1.05 µg/mL) activities were also high. Being the most active, the methanol fraction was subjected to bio-assay guided column chromatography-based enzyme inhibition to obtain a pure compound. The phenolic compound isolated and identified as naringenin inhibited α-amylase and α-glucosidase with IC<sub>50</sub> of 5.81 ± 2.14 µg/mL and 4.77 ± 2.99 µg/mL, respectively. This is the first study to isolate naringenin from <i>E. magalismontanum</i> extract. The molecular docking and molecular dynamics studies demonstrated naringenin as a promising lead compound in comparison to acarbose for the treatment of diabetes through the inhibition of α-glucosidase activity.
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