This study focuses on the efficient synthesis of series of substituted 4-amino-6-(1H-benzimidazol-2-ylsulfanyl) benzene-1,3-dicarbonitrile derivatives synthesized from aldehydes, propanedinitrile, substituted thiols and catalyzed by ZnO nanoparticles (ZnONPs). All the synthesized compounds have been characterized using different spectroscopic techniques such as FT-IR, ¹H-NMR, C¹³-NMR and Mass. The compounds were evaluated for potential pharmacological applications, including antimicrobial, α-amylase inhibitory and anticancer activities. Computational calculations, DFT, in-silico molecular docking, and ADME-toxicologystudies were performed. ADMET studies indicated that all synthesized compounds adhered to Rule of five with good bioavailability. This research underscores the promising pharmacological prospects of the synthesized newbenzimidazole derivatives.