Background <p>Microglia, the primary immune cells of the central nervous system, play a pivotal role in orchestrating neuroinflammatory responses and maintaining neural homeostasis. Post-translational modifications (PTMs) are critical regulators of microglial inflammatory activation, phagocytic capacity, and crosstalk with other neural cells.</p> Findings <p>This review highlights seven PTMs—phosphorylation, acetylation, methylation, ubiquitination, succinylation, SUMOylation, and lactylation—that are closely linked to the modulation of microglial inflammation. We discuss how these modifications shape microglial phenotypes during central nervous system diseases, particularly in the context of neuroinflammation, and explore their potential as therapeutic targets for inflammation-driven neuropathologies.</p> Implications <p>Understanding the regulatory landscape of PTMs provides valuable insights into microglial biology and the mechanisms underlying neuroinflammatory disorders. This review aims to summarize current evidence and offer a concise overview that may assist future research on PTM-mediated regulation of microglial function and its relevance to neurological diseases. </p>