<p>GlcNAcylation, a dynamic post-translational modification involving the addition of N-acetylglucosamine to serine and threonine residues, has emerged as a key regulatory factor in cellular metabolism and signaling. Ferroptosis, pyroptosis, and necroptosis are newly discovered forms of regulated cell death that play crucial roles in various physiological and pathological processes, including cancer development, neurodegeneration, and inflammation. This review aims to summarize the functions of O-GlcNAcylation in modulating these distinct cell death pathways, with a focus on their implications in disease mechanisms and potential therapeutic applications. We summarize the mechanisms by which O-GlcNAcylation modulates ferroptosis, pyroptosis, and necroptosis, and explore the potential of targeting O-GlcNAcylation as a promising therapeutic strategy for diseases characterized by dysregulated cell death.</p>