Microglia are the resident immune cells in the central nervous system (CNS), and play a dual role in maintaining brain homeostasis and mediating neuroprotection. Under normal conditions, microglia maintain brain homeostasis by monitoring environmental changes. When nerve damage or certain pathological stimuli occur, microglia are rapidly activated and initiate a series of complex immune responses to induce neuroinflammation. This proper activation of microglia can protect the brain by inhibiting or clearing various pathogens, but excessive neuroinflammation can lead to neuronal damage and even death. This imbalance of inflammatory response is one of the core features of pathological development of many CNS inflammatory diseases, such as Alzheimer′s disease, Parkinson′s disease, sepsis-associated encephalopathy, and ischemic strokes. In recent years, with the rapid development of frontier biotechnology such as single-cell sequencing, proteinomics and gene editing, important progress has been made in understanding the molecular mechanism by which microglia participate in CNS inflammatory diseases, especially in the activation of inflammatory corpuscles, epigenetic modifications, and metabolic reprogramming. However, due to the heterogeneity and duality of microglia under different pathological conditions, therapeutic methods targeting microglia have not yet been widely used in clinical practice. In summary, this article takes microglia as the starting point and introduces the molecular mechanisms of their involvement in the occurrence and development of CNS inflammatory diseases and its targeted regulatory treatment strategy, aiming to provide theoretical reference for the subsequent precise regulation of microglia function and the development of more targeted therapeutic drugs.