Phloroglucinol (PG) is a natural product isolated from plants, algae, and microorganisms. Aside from that, the number of PG derivatives has expanded due to the discovery of their potential biological roles. Aside from its diverse biological activities, PG and its derivatives have been widely utilized to treat microbial infections caused by bacteria, fungus, and viruses. The rapid emergence of antimicrobial-resistant microbial infections necessitates the chemical synthesis of numerous PG derivatives in order to meet the growing demand for drugs. This review focuses on the use of PG and its derivatives to control microbial infection and the underlying mechanism of action. Furthermore, as future perspectives, some of the various alternative strategies, such as the use of PG and its derivatives in conjugation, nanoformulation, antibiotic combination, and encapsulation, have been thoroughly discussed. This review will enable the researcher to investigate the possible antibacterial properties of PG and its derivatives, either free or in the form of various formulations.