**Background:** Oxidative stress, caused by an excess of free radicals, contributes to chronic diseases such as diabetes, cancer, and cardiovascular disorders. Diabetes, particularly type 2, affects over 95% of diabetic patients and is a major health burden globally, with Egypt having a 15.2% prevalence. α-Glucosidase inhibitors like acarbose delay carbohydrate digestion and reduce postprandial hyperglycemia. Plant-derived natural products are sought as safer alternatives to synthetic drugs. Dypsis pembana (Arecaceae) is an ornamental palm with limited prior biological investigation. This study aimed to evaluate the in vitro antioxidant and antidiabetic activities of its leaf extracts and isolated compounds, supported by molecular docking.
**Methods:** Dried leaves (5 kg) were extracted with 70% methanol to yield 870 g crude extract, which was partitioned into n-hexane (64 g), dichloromethane (CH2Cl2, 37 g), ethyl acetate (EtOAc, 30 g), and aqueous (700 g) fractions. Thirteen compounds were previously isolated, including flavonoids (kaempferol, quercetin, rutin, isoquercetrin, kaempferol-3-O-neohesperidoside, etc.). Antioxidant activity was assessed using the DPPH radical scavenging assay, with IC50 values calculated from dose-response curves. Antidiabetic activity was measured by α-glucosidase inhibition using p-nitrophenyl-α-D-glucopyranoside as substrate, with acarbose as standard. Molecular docking was performed using MOE 2020.01 on cytochrome c peroxidase (PDB: 2x08) and α-glucosidase (PDB: 3wy1) to evaluate binding affinities and interactions.
**Key Results:** The crude extract showed the highest antioxidant activity (IC50 11.56 µg/ml), followed by the EtOAc fraction (IC50 14.20 µg/ml). Among isolated compounds, isoquercetrin (10) was most potent (IC50 3.30 µg/ml), then rutin (8) (IC50 3.61 µg/ml), and quercetin (5) (IC50 4.75 µg/ml), compared to ascorbic acid (IC50 10.22 µg/ml). For antidiabetic activity, the EtOAc fraction (IC50 60.4 µg/ml) and CH2Cl2 fraction (IC50 214.9 µg/ml) were active; the crude extract and other fractions showed IC50 >1000 µg/ml. Among compounds, kaempferol-3-O-neohesperidoside (9) had the highest activity (IC50 18.38 µg/ml), followed by kaempferol (4) (IC50 37.19 µg/ml), while isoquercetrin (10) had IC50 91.29 µg/ml, and acarbose had IC50 3.12 µg/ml. Docking revealed that isoquercetrin (10) had the lowest binding score on cytochrome c peroxidase (−8.34 kcal/mol) and kaempferol-3-O-neohesperidoside (9) on α-glucosidase (−7.85 kcal/mol), consistent with in vitro results. Key interactions included hydrogen bonds with Arg184, Pro44, Val45 for peroxidase, and with Glu271, Asp333, Arg400 for α-glucosidase.
**Clinical Implications:** This study identifies isoquercetrin and kaempferol-3-O-neohesperidoside as promising natural lead compounds for antioxidant and antidiabetic therapies, respectively. The findings support the traditional use of Dypsis species and highlight the importance of flavonoid glycosylation patterns in biological activity. Further in vivo studies are needed to validate efficacy and safety before clinical translation. The results also provide chemotaxonomic markers for the Arecaceae family.