Anti-synthetase syndrome (ASS), a subtype of idiopathic inflammatory myopathy (IMM), is characterized by distinctive skin rashes, proximal muscle weakness, and interstitial lung disease (ILD). The etiology of ASS remains largely unknown, and patients endure a poor quality of life and are prone to pulmonary infection. Recent studies have highlighted the potential role of aberrant glycosylation of immunoglobulin G (IgG) in the development of autoimmune diseases. However, the specific N-glycosylation patterns of IgG in ASS have not yet been fully elucidated. In this study, we employed GlycoQuant, a method for intact glycopeptide analysis, to investigate the intact N-glycopeptides of IgG from 30 ASS patients and 30 healthy controls (HC). Our analysis revealed 13 differentially expressed intact N-glycopeptides in ASS. Furthermore, we observed a significant increase in fucose alongside a marked decrease in N-acetylneuraminic acid levels among ASS patients. Crucially, alterations in IgG N-glycosylation correlated with the disease severity. In conclusion, this study provides a thorough overview of IgG N-glycosylation patterns in ASS, laying a solid foundation for future research in this area.