Cancer is the second leading cause of death today and remains a threat to human health. The advent of multi-drug resistance and adverse effects make the current first-line anti-cancer medicines inadequate, despite the fact that numerous efforts have been made in the field of cancer therapy and significant progress has been made in the diagnosis and treatment of cancer. Consequently, the development of novel anticancer drugs with high activity and minimal toxicity is imperative. The benzimidazole ring has attracted the attention of medicinal chemists due to its medicinal and pharmacological properties. The heterocyclic pharmacophore of benzimidazole is a crucial scaffold for developing pharmaceuticals and drugs. In this review, we summarized the recent progress of benzimidazole as a privileged scaffold for the discovery of anti-cancer agents based on biological targets, such as VEGFR (Vascular Endothelial Growth Factor), PI3 K inhibitors (Phosphoinositide 3-kinase), EGFR kinase inhibitors (Epidermal Growth Factor Receptor), PARPs (Poly ADP-ribose polymerases), Tubulin Polymerization, HAT/HDAC (histone acetylase/histone deacetylase), SphK1 (Sphingosine kinase-1 inhibitors), aromatase, carbonic anhydrase, and topoisomerase inhibitors. The last 5 years of literature have been reviewed and relevant studies have been summarized in this review.