Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a critical global health issue with significant cases and deaths reported annually. The emergence of drug-resistant TB strains like multidrug- and extensively drug-resistant (M/XDR) TB exacerbates the challenge, necessitating more efforts in drug discovery approaches. One promising target for drug development is Shikimate Kinase (MtSK), a key enzyme in the shikimate pathway that is essential for the biosynthesis of aromatic amino acids and other key metabolites. This study explored the potential inhibitory activity of 1137 plant-derived compounds from the HerbalDB database against MtSK through pharmacophore modeling, molecular docking, molecular dynamics simulation, and ADMET analysis. Chlorogenic acid and sinigrin emerged as the top candidates, exhibiting strong binding affinities and favorable interactions with key residues in the MtSK active site. Molecular dynamics simulations confirmed the stability of these compounds within the active site, while ADMET and druglikeness evaluations further highlighted their potential as drug candidates. These findings suggest that plant-derived compounds, particularly chlorogenic acid and sinigrin, could be developed as inhibitors of MtSK, contributing to the fight against drug-resistant TB.