Eighteen new cobalt(II) or zinc(II) complexes of benzimidazole bearing 1-benzyl and 2-phenyl moieties were synthesized from the reaction of appropriate benzimidazole ligands and CoCl2 or ZnCl2. Their structural characterizations were done by IR, NMR (1H, 13C) and UV–VIS spectrometers. Cytotoxic activities of eighteen new complexes and three benzimidazole ligands were determined using A-2780 (human ovarian) and DU-145 (human prostate) cell lines. Antitumor properties of all compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell viability assay for the tested benzimidazole derivatives was performed and the LogIC50 values of the compounds were calculated after a 24-hour treatment. All tested benzimidazole derivatives showed higher or comparable antitumor activity against A-2780 cell lines compared to the standard drug docetaxel with a LogIC50 value of −0.81 µM (p < 0.05). Eight of the examined compounds (1, 3, 5, 6, 7, 9, 10 and 13) showed high cytotoxic activity against A-2780 compared to the standard drug docetaxel. While the LogIC50 of the docetaxel was −0.81 µM for A-2780 cells at 24 h, the IC50 values of compounds 1, 3, 5, 6, 7, 9, 10 and 13 were −0.97, −1.30, −0.22, 0.13, −0.16, −0.73 and −0.53 µM, respectively. Three of the compounds 1, 18 and V showed high cytotoxic activity against DU-145 compared to docetaxel (p < 0.05). While the LogIC50 of the docetaxel was −1.13 µM for DU-145 cells at 24 h, the LogIC50 values of compounds 1, 18 and V were 0.84, −0.38 and −0.66 µM, respectively.