Piperine is an attractive target from natural sources for designing of novel compounds for many pharmacological activities. In present work, series of MAO inhibitors were taken and QSAR models were generated using MLRA. The best model were validated using test set, they exhibited r2 0.8427 and q2 0.7852 for MOA-B inhibitors; MAO-A inhibitors showed r2 0.7970 and q2 0.6657. Models. The QSAR models were used to design 70 new piperine analogue and docking studies were performed to check their inhibitory activity. Docking studies were performed using AutoDock, with proteins 2BXR and 2VZ2 for MAO-A and MAO-B inhibitory activity respectively. P12 and P11 for 2BXR showed best binding energy of -5.89 kcal/mol. and -6.43 kcal/mol respectively whereas P1078 and P1090 showed binding energy of -5.86 kcal/mol. and -8.56 kcal/mol for 2VZ2 respectively.