Efforts were made to synthesize a series of substituted methoxybenzyl-sulfonyl-1H-benzo[d]imidazole derivatives (8a-l) and investigate their anti-ulcer therapeutics. Prior to evaluating antiulcer potentials of 8a-l, a preliminary binding assay against H+/K+-ATPase from goat gastric mucosa was carried out, since it plays an important role in the ulcer development. In order to get more insight into the binding mode of the compounds to H+/K+-ATPase, a molecular docking study was carried out and the best binding affinities were unveiled. Many of the substituted methoxybenzyl-sulfonyl-1H-benzo[d]imidazole derivatives (8a-l) were active for the proposed activity. The key finding was that, least inhibitory constant (ki) values of 8a-l were found between 0.02 and 1.8 μM in the molecular docking study. Almost the same range was reflected/correlated in the H+/K+-ATPase inhibition assay (IC50 0.14-1.29 μM). Remarkably, compounds 8a-l showed a relative activity percentage range of 72-92%. Efficient HRBC membrane stabilization activity of 8a-l ensured the non-harm/safety and the suitability/alternative towards anti-ulcer therapy.