Neurological disorders are disorders characterized by progressive loss of neurons leading to disability. Neurotransmitters such as nor-adrenaline, dopamine, and serotonin are partially regulated by the enzyme monoamine oxidase (MAO). Treatments for conditions like Alzheimer’s, Parkinson’s, anxiety, and depression involve the use of MAOIs. To target MAO enzyme inhibition, various scaffolds are prepared and evaluated, including modified coumarins, chromone carboxylic acid substituents, pyridazine derivatives, and indolylmethylamine. The research presented here focuses on combining different computational tools to find new inhibitors of the MAO-B protein. We discovered 5 possible chemical inhibitors using the above computational techniques. We found five molecular inhibitors with high binding affinity using computational methods. These five molecules showed a high binding affinity; they are −10.917, −10.154, −10.223, −10.858, and −9.629 Kcal/mol, respectively. Additionally, the selected inhibitors were further examined by in vitro activity, and their binding affinity was confirmed using an enzyme-based assay. In summary, the computational studies performed here using molecular dynamics and free energy calculations can also be used to design and predict highly potent derivatives as MAO-B inhibitors, and these top inhibitors help in the development of novel drugs for neurological diseases such as Alzheimer’s and Parkinson’s.