The present study aimed to identify the prospective inhibitors of MurD, a cytoplasmic enzyme that catalyzes the addition of d-glutamate to the UDP-N-acetylmuramoyl-l-alanine nucleotide precursor in Mycobacterium tuberculosis (MTB), using virtual screening, docking studies, pharmacokinetic analysis, Molecular Dynamic (MD) simulation, and Molecular Mechanics Generalized Born and Surface Area (MM-GBSA) analyses. The three dimensional (3D) structure was determined based on the homology technique using a template from Streptococcus agalactiae. The modeled structure had three binding sites, namely; substrate binding site (Val18, Thr19, Asp39, Asp40, Gly75, Asn147, Gln171 and His192), the ATP binding site (Gly123, Lys124, Thr125, Thr126, Glu166, Asp283, and Arg314) and the glutamic acid binding site (Arg382, Ser463, and Tyr470). These residues mentioned above play a critical role in the catalytic activity of the enzyme, and their inhibition could serve as a stumbling block to the normal function of the enzyme. A total of 10,344 obtained from virtual screened of Zinc and PubChem databases. These compounds further screened for Lipinski rule of five, docking studies and pharmacokinetic analysis. Four compounds with good binding energies (ZINC11881196 = -10.33 kcal/mol, ZINC12247644 = -8.90 kcal/mol, ZINC14995379 =-8.42 kcal/mol, and PubChem6185 = -8.20 kcal/mol), better than the binding energies of the ATP (-2.31 kcal/mol) and the ligand with known IC, Aminothiazole (-7.11 kcal/mol) were selected for the MD simulation and MM-GBSA analyses. The result of the analyses showed that all the four ligands formed a stable complex and had the binding free energies better than the binding energy of ATP. Therefore, these ligands considered as suitable prospective inhibitors of the MurD after experimental validation.