Sialic acids, predominantly found at the terminal ends of glycoproteins and glycolipids, play crucial roles in cellular communication and function. Sialylation, a post-translational modification involving the covalent attachment of sialic acid to these molecules, provides electrostatic repulsion and serves as a receptor for various biological signaling pathways. This review highlights the biological functions of sialic acids and sialylation, their roles in various pathophysiological contexts, and their potential applications in therapeutic interventions. Sialic acids are negatively charged, nine-carbon monosaccharides that are essential for maintaining the biophysical properties of cells, such as preventing erythrocyte adhesion and facilitating their transit through the circulatory system. Sialylation also plays a key role in intercellular signaling through specific ligands like sialic acid-binding immunoglobulin-like lectins (SIGLECs) and selectins. The process of sialylation is regulated by sialyltransferases and sialidases, with sialyltransferases catalyzing the addition of sialic acid and sialidases mediating its removal. In physiological processes, sialylation is involved in immune responses, complement activation, and protein conformation regulation. In pathological processes, sialylation is implicated in cancer progression, metastasis, immune evasion, neurological disorders, cardiovascular diseases, and virus infection. For example, hypersialylation in tumor cells enhances their resistance to apoptosis and promotes proliferation, while sialylation in the central nervous system is crucial for maintaining stem cell pluripotency and sperm development. Therapeutic strategies targeting sialic acid residues or the sialylation process are being explored, particularly in cancer therapy, stroke treatment, antiviral strategies, and therapies for central nervous system disorders. These strategies include developing drugs that disrupt sialic acid metabolism, inhibiting sialyltransferases, targeting sialic acid-ligand interactions, and conjugating antibodies with sialidase. The review also discusses the potential benefits and challenges of these approaches, as well as unresolved questions about the effects of aberrant sialic acid metabolism on cellular activities.Sialic acids, predominantly found at the terminal ends of glycoproteins and glycolipids, play crucial roles in cellular communication and function. Sialylation, a post-translational modification involving the covalent attachment of sialic acid to these molecules, provides electrostatic repulsion and serves as a receptor for various biological signaling pathways. This review highlights the biological functions of sialic acids and sialylation, their roles in various pathophysiological contexts, and their potential applications in therapeutic interventions. Sialic acids are negatively charged, nine-carbon monosaccharides that are essential for maintaining the biophysical properties of cells, such as preventing erythrocyte adhesion and facilitating their transit through the circulatory system. Sialylation also plays a key role in intercellular signaling through specific ligands like sialic acid-binding immunoglobulin-like lectins (SIGLECs) and selectins. The process of sialylation is regulated by sialyltransferases and sialidases, with sialyltransferases catalyzing the addition of sialic acid and sialidases mediating its removal. In physiological processes, sialylation is involved in immune responses, complement activation, and protein conformation regulation. In pathological processes, sialylation is implicated in cancer progression, metastasis, immune evasion, neurological disorders, cardiovascular diseases, and virus infection. For example, hypersialylation in tumor cells enhances their resistance to apoptosis and promotes proliferation, while sialylation in the central nervous system is crucial for maintaining stem cell pluripotency and sperm development. Therapeutic strategies targeting sialic acid residues or the sialylation process are being explored, particularly in cancer therapy, stroke treatment, antiviral strategies, and therapies for central nervous system disorders. These strategies include developing drugs that disrupt sialic acid metabolism, inhibiting sialyltransferases, targeting sialic acid-ligand interactions, and conjugating antibodies with sialidase. The review also discusses the potential benefits and challenges of these approaches, as well as unresolved questions about the effects of aberrant sialic acid metabolism on cellular activities.