Introduction: The main objective of this research is to identify potential leads for developing potent Keap1 inhibitors. Methods: In the current research article, Results: The virtual screening of different databases was carried out separately and three leads, were obtained. These lead molecules ASINEX 508, MiniMaybridgeHTS_01719, and ZINC 0000952883 showed the best binding in the Keap1 cavity. The molecular dynamic simulations of the binding complexes of the leads support the docking analysis. The leads (ASINEX 508, MiniMaybridgeHTS_01719, and ZINC 0000952883) were stabilized in the Keap1 binding cavity throughout 100 ns simulation, with average RMSD values of 0.100, 0.114, and 0.106 nm, respectively. Conclusion: This research proposes three lead molecules as potential Keap1 inhibitors based on high throughput screening, docking, and MD simulation studies. These hit molecules can be used for further design and development of Keap1 inhibitors. This research provides the preliminary data for discovering novel Keap1 inhibitors. It opens new avenues for medicinal chemists to explore antioxidant-stimulating molecules targeting the Keap1-Nrf2 pathway.