The benzimidazole core (BI) plays a central role in biologically active molecules. The BI nucleus is widely used as a building block to generate a variety of bioactive heterocyclic compounds to be used as antihelmintics, antiprotozoal, antimalarials, anti-inflammatories, antivirals, antimicrobials, antiparasitics, and antimycobacterials. A versatile BI derivative is the 2-guanidinobenzimidazole (2GBI), which, together with its derivatives, is a very interesting poly-functional planar molecule having a delocalised 10 π electrons system conjugated with the guanidine group. The 2GBI molecule has five nitrogen atoms containing five labile N-H bonds, which interact with the out-ward-facing channel entrance, forming a labile complex with the biological receptor sites. In this work, 2GBI and their derivatives were analyzed as ligands to form host-guest, coordination and organometallic complexes. Synthesis methodology, metal geometries, hydrogen bonding (HB) interactions, and the biological activities of the complexes were discussed.