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Diabetes mellitus is a widespread metabolic disorder characterized by impaired glucose regulation. This study investigated the chemical composition and antidiabetic potential of Origanum majorana essential oil (EO) using integrated in vitro, in vivo, and computational approaches. GC-MS analysis identified 42 constituents representing 96.28% of the oil, with trans-thujone (33.30%), santolina triene (16.42%), and cis-verbenyl acetate (15.05%) as the dominant components. In vitro assays revealed strong inhibitory activity against carbohydrate-hydrolyzing enzymes, with IC₅₀ values of 3.68 µg/mL for α-amylase and 4.71 µg/mL for α-glucosidase, which were lower than those of the reference drug acarbose (11.17 and 9.68 µg/mL, respectively). In vivo evaluation in alloxan-induced diabetic rats demonstrated a significant reduction in fasting blood glucose levels from 1.47 ± 0.04 g/L in the diabetic group to 0.94 ± 0.03 g/L after EO treatment, accompanied by improvements in biochemical and histopathological parameters. Molecular docking identified several major EO constituents with strong binding affinities toward α-amylase and α-glucosidase, particularly cis-verbenyl acetate (-6.64 and -7.27 kcal/mol) and β-pinene oxide (-5.40 and -6.46 kcal/mol), exceeding the affinity of acarbose. ADMET analysis predicted favorable pharmacokinetic profiles and low toxicity risks for these compounds. Molecular dynamics simulations confirmed stable protein-ligand interactions, while MM-PBSA calculations supported strong binding free energies. Density functional theory (DFT) analysis further revealed moderate reactivity and enhanced stability in aqueous environments. Overall, the combined experimental and computational findings suggest that O. majorana EO, particularly its constituents cis-verbenyl acetate and β-pinene oxide, represents a promising natural source of antidiabetic agents warranting further pharmacological investigation.