Resveratrol is known as anti-metabolic syndrome agent, occuring naturally in some plants as phytoalexin group. Resveratrol and its derivate has been successfully isolated from melinjo (Gnetum gnemon L.). Melinjo seed extract has been reported with many biological activities including antioxidant, antidiabetic, anticancer, antiinflammatory effect, antibacterial, and lipase-amylase inhibition. The research aimed to analyze HMG CoA reductase inhibitory activity and resveratrol assay quantification from melinjo seed extracts. Dried melinjo seeds were successively extracted by reflux method using five solvents with gradient polarity. Each of extracts was tested using HMG CoA Reductase Assay Kit Sigma Aldrich ©, to analyzed the inhibition activity. Ethyl acetate extract showed their highest resveratrol assay in amount of 8190, 3184, 686 mg/kg dried seed. On the other hand, dichloromethane extract gave result as the highest inhibitory activity against HMG CoA Reductase with IC₅₀ value is 0.4037 µg/mL. Further, dichloromethane extract subjected to UPLC-MS to define the exact constituent which are responsible for its inhibition. Results showed that resveratrol, gnetin C, epsilon-viniferin and gnetifolin K, gnemonoside A/B appeared in dichloromethane extract. Additionally, molecular docking is also being done to figured out the active ligand-binding site HMG CoA reductase. LigandScout is used to perform test sets including interaction energy calculations, ligand-based pharmacophore, and 3D chemical features. In conclusion, dichloromethane extract of Gnetum gnemon L. seed might suggest its role in inhibiting HMG CoA reductase activity.