Smilax zeylanica is a medicinal plant native to Southeast Asia that has been used for centuries to treat a variety of ailments, including hyperlipidemia. However, the mechanisms underlying its antilipidemic effects are not fully understood. In this study, we performed metabolomic profiling of S. zeylanica roots extracts and screened for potential antilipidemic compounds using in vitro and in silico methods. Metabolomic analysis using spectral and Chromatographic techniques such as GSMS and HPLC revealed that S. zeylanica roots contain a variety of metabolites, including flavonoids, phenolic acids namely gallic acid, chlorogenic acid, Quercetin and several other potent phytoconstituents. In vitro pancreatic lipase assays, HMGCoA reductase assay showed that S. zeylanica root extract significantly showed inhibitory potential at par with the standard drug orlistat and atorvastatin respectively. Molecular docking studies showed that several of the metabolites identified in S. zeylanica roots, including quercetin, kaempferol, and gallic acid, etc bind to the HMG-CoA reductase enzyme, a key enzyme in cholesterol biosynthesis. These findings suggest that S. zeylanica may exert its antilipidemic effects by inhibiting HMG-CoA reductase activity. Overall, this study provides new insights into the metabolomic profile of S. zeylanica and its potential antilipidemic activity. Further studies are needed to elucidate the specific mechanisms underlying its antilipidemic effects and to confirm its safety and efficacy profiles.