Background: Aldosterone antagonists (spironolactone, eplerenone) inhibit the action of aldosterone in the collecting duct; as such, these agents cause modest diuresis but inhibit potassium and hydrogen ion secretion. We report first time Potential Aldosterone antagonists by in Silico approach, using AutoDock Vina and AutoDock 4 (or MGL Tool), estimated with Pyrx and AM Dock Software, calculating three different important parameters: Binding Affinity ( kcal/mol), estimated Ki ( in nM units) and Ligand Efficiency ( L.E. in kcal/mol). After a selective analysis of over 1000 drugs, processed with Pyrx (a Virtual Screening software for Computational Drug Discovery) in the Ligand Binding site pocket of the protein ( ID PDB 2OAX Chain A:), we noticed high values of Binding Energy , about -13.55 kcal/mol estimated by AutoDock 4 with AM Dock Software, concluding that it could be an excellent candidate drug, compared to everyone else Aldosterone antagonists. Indeed, from the results of AutoDock Vina and AutoDock 4 ( or AutoDock 4.2 ), implemented with Lamarckian genetic algorithm, LGA, trough AMDock Software, our results of Binding Energy are very similar to the crystallized Spironolactone in PDB 2OAX Chain A protein.