<p>The heterocyclic moiety benzimidazole holds significant importance as a primary “biolinker” in various synthetic strategies employed for the development of bioactive compounds. Substituted benzimidazoles are widely recognized for their broad spectrum of therapeutic applications, including anticancer, antidiabetic, anti-inflammatory, and antiviral activities, such as anti-HIV and antifungal effects. Similarly, thiophene derivatives exhibit a wide range of pharmacological activities and serve as essential structural components in numerous pharmaceuticals. The diverse bioactivities of newly synthesized thiophene compounds underscore their critical role in pharmaceutical research. Thiophene clubbed with benzimidazole represents an interesting area of research in pharmaceuticals, particularly due to its potential applications and its discussion is limited. The structural diversity of thiophene and benzimidazole creates a novel molecular framework and is essential for the development of new compounds with improved efficacy. The fusion of these two structures could enhance their biological activity and broaden their applications in pharmaceutical chemistry. In addition, their synthetic versatility can lead to a variety of functionalized compounds. Given the complementary properties of benzimidazole and thiophene, this review highlights the recent advancements in the synthesis and potential applications of thiophene-based benzimidazole derivatives. Further, the novelty of thiophene clubbed benzimidazole structures throws light on its mechanism of action, structure-activity relationship and synergistic effects.</p> Graphical abstract <p></p>