•The anti-diabetic effects of Chamaerops humilis methanol extract (CHME) and five identified compounds named: tricin-7-rutinoside (1), tricin (2), dihydrotricin (3), (salcolin A) (4a), (salcolin B) (4b), and (-)-(5s, 6s)-5,6-dihydro-3,8,10-trihydroxy-5-(4-hydroxy-3-methoxyphenyl)-6-hydroxymethyl-2,4-dimethoxy 7H benzo e xanthen-7-one (5) were evaluated in-vivo and in-vitro.•The beneficial activities of CHME were attributed to its phenolic content.•CHME extract exhibited an antidiabetic effect by controlling hyperglycaemia and reducing the inflammatory response including TNF-α, IL6, and MMP-1, were downregulated by CHME treatment.•Molecular docking simulations indicated that compounds 1, 2, and 3 had higher binding energies compared to the reference drug acarbose when tested against α-glucosidase and α-amylase. Five compounds were isolated from the aerial parts of Chamaerops humilis L. and characterized as tricin-7-rutinoside (1), tricin (2), dihydrotricin (3) diasteroisomer of tricin 4′-O(erythro-β-guaiacyl glyceryl) ether (salcolin A)(4a), tricin-4′-O-(threo-β-guaiacyl glyceryl) ether (salcolin B) (4b) and (-)-(5s, 6s)-5,6-dihydro-3,8,10-trihydroxy-5-(4-hydroxy-3-methoxyphenyl)-6-hydroxymethyl-2,4-dimethoxy 7H benzo e xanthen-7-one (5). Their structures were elucidated by comparing their spectral data with those reported in the literature. To the best of our knowledge, compounds (3-5) were reported here for the first time from Chamaerops humilis. The methanolic extract of Chamaerops humilis (CHME) and the five isolated compounds were studied for its anti-diabetic effect using in vitro α-glucosidase and α-amylase inhibitory assay that showed a significant activity. The toxicological study indicated that CHME was safe up to 5000 mg/kg bw. Two doses were selected for the in vivo study (800 and 1600 mg/kg bw) and orally administered to high fat diet/streptozotocin-induced diabetic rats for 10 consecutive days. The results revealed that the CHME improved the blood glucose levels in a dose dependent manner, the dose 1600 mg/kg showed the best results dependently along the period of the experiment. CHME and the five isolated compounds were evaluated in silico for their anti-diabetic effect. The anti-inflammatory effect of CHME (1600 mg/kg bw) was proved by significant downregulation of expression for interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-1 (MMP-1) genes. In conclusion, CHME and its constituents may be a potential hypoglycemic agent working through the anti-inflammatory and enzyme inhibitory pathways. The docking studies demonstrated that compounds Tricin7-rutinoside and Salcolin isomers had promising binding energies of -9.10 kcal/mol and -8.70 kcal/mol, respectively, against α-amylase. These binding energies were superior to that of acarbose, which had a binding energy of -7.60 kcal/mol. In addition, docking analysis provided promising results for the inhibition of α-glucosidase by Tricin7-rutinoside and Dihydrotricin with binding affinity -7.9 kcal/mol and -7.9 kcal/mol, respectively while the binding affinity of acarbose is -6.40 kcal/mol. Overall, the methanolic extract from Chamaerops humilis exhibited good in silico of α-amylase and α-glucosidase enzyme inhibition potential. These findings suggest that these compounds may have potential as anti-diabetic agents, with further research needed to verify their efficacy and safety.