A new series of benzimidazole-oxadiazole-small molecules were synthesized and confirmed with various spectroscopic techniques. The prepared derivatives exhibited significant inhibitory activity against the proliferation of different cancer cells. The benzimidazoles 10f, 10 h, 10 g, and 10i showed broad anticancer activity with no selectivity in five-dose assays. All prepared compounds displayed potent inhibitory activity against proliferation of a panel of four human cancer cells (HT-29, Panc-1, MCF-7, and A-549) with IC