Background: Oxidative stress and diabetes are medical conditions that have a growing prevalence worldwide, significantly impacting our bodies. Thus, it is essential to develop new natural antioxidant and antidiabetic agents. Dypsis pembana (H.E.Moore) Beentje & J.Dransf (DP) is an ornamental palm of the family Arecaceae. This study aimed to broaden the understanding of this plant's biological properties by evaluating its in vitro antioxidant and antidiabetic activities.

Methods: The in vitro antioxidant activities of the crude extract, fractions, and selected isolates were evaluated by DPPH method. While the in vitro antidiabetic activities of these samples were evaluated by assessing the degree of inhibition of α-glucosidase. Additionally, molecular docking analysis was performed to investigate the interactions of tested compounds with two potential targets, the cytochrome c peroxidase and alpha glucosidase.

Results: The crude extract displayed the highest antioxidant activity (IC₅₀ of 11.56 µg/ml), whereas among the fractions, the EtOAc fraction was the most potent (IC₅₀ of 14.20 µg/ml). Among tested compounds, isoquercetrin (10) demonstrated the highest potency, with an IC₅₀ value of 3.30 µg/ml, followed by rutin (8) (IC₅₀ of 3.61 µg/ml). Regarding antidiabetic activity, the EtOAc (IC₅₀ of 60.4 µg/ml) and CH₂Cl₂ fractions (IC₅₀ of 214.9 µg/ml) showed activity, while the other fractions did not demonstrate significant antidiabetic effects. Among tested compounds, kaempferol-3-O-neohesperidoside (9) showed the highest antidiabetic activity, with an IC₅₀ value of 18.38 µg/ml, followed by kaempferol (4) (IC₅₀ of 37.19 µg/ml). These experimental findings were further supported by molecular docking analysis, which revealed that isoquercetrin and kaempferol-3-O-neohesperidoside exhibited strong enzyme-binding affinities to the studied enzyme targets. This analysis provided insights into the structure-activity relationships among the investigated flavonol-O-glycosides.

Conclusion: The biological and computational findings revealed that isoquercetrin and kaempferol-3-O-neohesperidoside have potential as lead compounds for inhibiting cytochrome c peroxidase and alpha glucosidase enzymes, respectively.