The unprecedented coronavirus SARS-CoV-2 outbreak at Wuhan, China caused acute respiratory infection to humans. There is no precise vaccine/therapeutic agents available to combat the COVID-19 disease. Some repurposed drugs are saving the life of diseased, but the complete cure is relatively less. Several drug targets have been reported to inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (Transmembrane protease serine 2) is one of the potential targets, inhibiting this protease stops the virus entry into the host human cell. Camostat mesylate, nafamostat and leupeptin are the drugs, in which the first two drugs are being used for COVID-19 and leupeptin also tested. To consider these as repurposed drugs for COVID-19, it is essential to understand their binding affinity and stability with TMPRSS2. In the present study, we performed the molecular docking and molecular dynamics (MD) simulation for the three molecules with the TMPRSS2. The docking study reveals that leupeptin molecule strongly binds with TMPRSS2 protein than the other two drug molecules. The RMSD and RMSF values of MD simulations shows, leupeptin and the amino acids of TMPRSS2 are very stable than the other molecules. Furthermore, leupeptin forms interactions with the key amino acids of TMPRSS2 and the same have been maintained during the MD simulations. This structural and dynamical information is useful to evaluate these drugs to be used as repurposed drugs, however, the strong binding profile of leupeptin with TMPRSS2, suggests, it may be considered as a repurposed drug for COVID-19 after clinical trial.