Aldosterone synthase inhibitors can lessen the production of aldosterone in organisms, which effectively affecting the treatment of hypertension. A series of computational approaches like QSAR, docking, DFT and molecular dynamics simulation are applied on 40 benzimidazole derivatives of aldosterone synthase (CYP11B2) inhibitors. Statistical parameters: Q² = 0.877, R² = 0.983 (CoMFA) and Q² = 0.848, R² = 0.994 (CoMSIA) indicate on good predictive power of both models and DFT’s result illustrates the stability of both models. Besides, Y-randomization test is also performed to ensure the robustness of the obtained 3D-QSAR models. Docking studies show inhibitors rely on π-π interaction with residues, such as Phe130, Ala313 and Phe481. Molecular dynamics simulation results further confirm that the hydrophobic interaction with proteins enhances the inhibitor’s inhibitory effect. Based on QSAR studies and molecular docking, we designed novel compounds with enhanced activity against aldosterone synthase. Furthermore, the newly designed compounds are analyzed for their ADMET properties and drug likeness and the results show that they all have excellent bioavailability.