Abstract: Obesity has become a world-wide health concern. Natural products and Chinese herbs are popular alternatives for weight reduction however the mechanism of actions remains unclear. Slimming plus (SP) formula is a Chinese herbal formula modified from RCM104, which was previously proven to be effective for weight reduction in the clinical trial by our research team. The aim for this study is to investigate the mechanisms of the SP formula and provide scientific rationale for its effectiveness. Methods: 73 compounds/ligands and 2 targeted proteins (pancreatic lipase and amylase) were chosen from literature review. Autodock software Pyrx was used for virtual molecular screening, which can predict the interactions between the ligands and targeted proteins. In addition, SP formula was qualitatively analysed via high-performance thin-layer chromatography (HPTLC) against 10 bioactive chemical references that are known for weight-loss. Results: Molecular docking showed that the main chemical components from each herb of SP formula have higher binding affinities (kcal/mol) compared to the control Orlistat and Acarbose (lipase and amylase inhibitor respectively). The leading compounds for the target proteins have been predicted as chrysophanol, caffeine, genisterin, gallic acid, genipin, alismol, catapol, eburicoic acid according to their efficiency scores, which are almost twice as high as that of the control. HPTLC results indicated that the SP formula contains bioactive compounds for weight reduction such as epigallocatechin gallate (EGCG), caffeine etc. Conclusion: Molecular docking and HPTLC have preliminarily explored the potential mechanisms of the SP formula for weight reduction. Further studies such as inhibition assays will be followed for verifying the lipase and amylase inhibitory activities of the SP formula.