ABSTRACT Swertiamarin has a potential for treating metabolic illnesses, Parkinson’s disease, and its hepatoprotective and antiaging effects are evident. In spite of high yield in herb Enicostemma littorale Blume, the complexity of phytochemical makeup of extract presents difficulties in purification of swertiamarin due to a closely eluting flavonoid glycoside(s) and has an impact on the final output. At the laboratory scale, advanced techniques such as centrifugal partition and counter-current chromatography have been examined. However, feasibility of scaling up these strategies is limited. We developed a four-step SpPRE technique for enriching swertiamarin in the extract which includes optimization of Solvent for extraction, liquid-liquid partitioning, Precipitation, and Resin Enrichment step. This technique enabled enrichment of swertiamarin from 10.9% to 81.7% with reduction in extract weight by 91%. Subsequently, a single-step silica gel column chromatography resulted into 97% pure swertiamarin. The SpPRE methodology has resolved the problem of repeated column chromatography as well as the sample loading over to silica gel. To determine the concentration of the compound at each step, a validated HPLC method was employed. Furthermore, the current approach’s ability to isolate the target component in a high yield will increase swertiamarin’s market value and research prospects.