The project work involves the development and computational investigation of 2-phenoxyacetamide derivatives as MAO -B inhibitors. A series of 28 compounds based on 2-phenoxyacetamide derivatives were selected for the construction of the 2D QSAR model. The QSAR model was constructed using Chem Office 2002 and VALSTAT 6.0. The model was validated based on various statistical parameters and was able to significantly predict the biological activity of the compounds from the “test set” and the “training set”. The reported experimental IC50 value was used as the biological data set for the development of the QSAR model. A total of 75 new molecules were designed by varying the different substituents on the 3-phenoxyacetamide scaffold. All designed molecules were subjected to the calculation of the molecular descriptors involved in the construction of the QSAR model (PMI-Y, PMI-Z), followed by the prediction of the biological activity for each of them. Of the total 75 designed molecules, 40 molecules with comparable predicted biological activity were subjected to molecular docking analysis along with a standard ligand using the AutoDock module of PyRx software to determine their binding efficacy and interaction with target protein i.i.e. MAO -B (PDB ID 4CRT), out of all 40 ligands docked, a total of 20 ligands showed good electrostatic and hydrophobic interaction with the active site residues of MAO -B protein(4crt), and they have better docking score compared to the standard ligand (rasagiline) docked. Going forward, a PreADMET study was performed for all 20 ligands that showed promising results in docking analysis using the web-based online application Pre-ADMET. The PreADMET study directly correlated the pharmacokinetic and toxicological properties of the molecules. Of the 20 ligands subjected to the PreADMET study, ligand “9G” showed the best pharmacokinetic profile, including the ability to cross the BBB, and it showed negative results in terms of toxicity in rat and mouse.