As a second messenger widely present in bacteria, cyclic diguanosine monophosphate (c-di-GMP) can act on differ ent receptors to regulate various physiological functions of bacteria, including biofilm formation, bacterial motility, bacterial virulence, cell cycle and differentiation. The enzymes responsible for the synthesis and degradation of c - di - GMP are diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), respectively. The diguanylate cyclase contains a GGDEF conserved domain, and the phos phodiesterase contains an EAL conserved domain or an HD-GYP domain. The level of intracellular c-di-GMP is dependent on the ac tivity of diguanylate cyclase and phosphodiesterase, and proteins containing the GGDEF and EAL/ HD-GYP domains are often linked to the signal-sensing regulatory domain at the N-terminus, such as PAS domain and REC domain. These regulatory domains are able to sense intracellular and extracellular signals to regulate intracellular c-di-GMP levels. In addition, protein interactions between c-di GMP synthesis and degrading enzymes and interactions with other proteins can also regulate. This paper reviews the mechanism of the second messenger c-di-GMP synthesis degradation and regulation mechanism, and summarizes the latest research progress.