In this study, we focused on the synthesis and molecular docking investigations of hybrid derivatives containing tetrahydrobenzo[b]thiophene. Our aim was to evaluate their potential antibacterial properties. Through our analysis, we aimed to gain insights into the molecular mechanisms that underlie their effectiveness against bacterial infections. A series of tetrahydrobenzo[b]thiophene derivatives were produced through the reaction of various carbonyl groups, including 2-thiophenaldehyde, 2-naphthaldehyde, and 3-acetylindole with (2-amino-N-(4-methoxyphenyl)-4-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carboxamide). Additionally, the condensing starting material with benzaldehyde, a new derivative linked to substituted pyrimidines was synthesized and named tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4,5-dione. Furthermore, it underwent a reaction with monochloroacetyl chloride to produce another derivative. The production and synthesis processes all involved the use of tetrahydrobenzo[b]thiophene compounds.