Background: Tuberculosis is a worldwide health concern, and there is an immediate need for effective therapeutics to inhibit the infection caused by Mycobacterium tuberculosis. The persistent state of bacteria and the emergence of Multi-Drug Resistance are the two major reasons for the difficulty in treating tuberculosis.Objective: The study aims to identify novel phytocompounds to effectively inhibit Mycobacterium tuberculosis by targeting the Esx-1 protein, which plays a vital function in the secretion pathway of M. tuberculosis to successfully disrupt the host cell and cause tuberculosis.Methods: In the current study, similar to 500 novel phytocompounds were screened by docking against Esx-1 using AutoDock Vina 4.2 version. The visualization analysis for selected phytocompounds was performed using Protein-Ligand Interaction Profiler. A comparative study with a well-known drug for tuberculosis, Rifampicin, was also performed. Moreover, ADMET analysis was performed to check the druggability and pharmacokinetic parameters of the selected compounds.Results: Based on the analysis, cadabicine, an alkaloid produced by Cadaba fruticose (Vizhuthi), Crataeva nurvala (Varuna) plants, exhibits the best binding affinity of -7.8 Kcal/mol with the active site residues, Leu 29 and Trp 43, of Esx-1, which are required for the stability of Esx-1 and virulence of M. tuberculosis in the host cell. ADMET analysis showed that cadabicine exhibits better druggability and pharmacokinetic parameters than other selected compounds.Conclusion: Cadabicine possesses an acceptable binding affinity with the active site of Esx-1 and exhibits acceptable physicochemical and pharmacokinetic properties, which makes it a potential new drug candidate for the treatment of tuberculosis.