Abstract:Background and Objectives: The present study was designed to assess the antileprotic effectiveness of some bioactive natural compounds towards enoyl acyl carrier protein reductase inhibition. Leprosy still constitutes a global pandemic in spite of long years of discovery. The current therapy option is multi-drug treatment using a combination of Dapsone, Rifampicin and Clofazimine. However, mycobacterium leprae counteracted by mutating the drug targets which necessitates the search for novel targets. One such target is enoyl acyl carrier protein reductase that mediates the fatty acid biosynthesis. Materials and Methods: Multiple (14) ligands of natural origin were drawn from PubChem database and their ADMET parameters were preicted using ADMETLab 2.0 webserver. After, the ligands were docked against the enzyme (PDB ID: 2NTV) at its active site using iGEMDOCK software. Results: ADMET parameters of the tested ligands proven to be accepted by Lipinski's rule of five except for two ligands. Furthermore, molecular docking results revealed that all of the tested compounds showed better binding energy than the reference drug Dapsone. The best of which was silymarin. Conclusion: The tested natural ligands have the capability to control M.leprae.