Protein glycosylation is a covalent attachment of complex oligosaccharides to proteins and lipids, is a ubiquitous and essential post-translational modification (PTM) that significantly expands the functional diversity of the proteome. While fundamental to processes such as protein folding, trafficking, and signal transduction, disruptions in normal glycosylation are increasingly recognized as central drivers of immune dysregulation and tissue damage. This review provides an overview of N- & O-linked glycosylation mechanisms and evaluates their profound influence on protein stability, activity, and the pathophysiology of common autoimmune disorders. This review focus on recent literature, focusing on the pathways of endoplasmic reticulum (ER) and Golgi apparatus, alongside advancements in mass spectrometry-based glycomics, to explore the relationship between altered glycan structures and clinical disease states. Specific glycans are identified as hallmarks of various conditions: Immunoglobulin G (IgG) agalactosylation in Rheumatoid Arthritis and IBD; increased sialylation and N-glycan bisection in Type 1 Diabetes; and elevated N-acetylglucosamine in Systemic Lupus Erythematosus; in Celiac Disease, we highlight the mechanistic role of galactose-deficient IgA1 and the mislocalization of the receptor in facilitating pathogenic antigen trafficking serving as sensitive biomarkers for disease activity and treatment adherence, glycan alterations actively modulate the inflammatory milieu. These glycosylation pathways offer a promising frontier for therapeutic intervention. Continued integration of glycomics into personalized medicine is essential for improving the diagnostic and prognostic accuracy for patients suffering from multisystemic autoimmune diseases. published by the International Journal of Biosciences | IJB