This study investigated the glycoproteomic alterations associated with the development of CHD in patients with T2DM, with a particular focus on dual-layer changes in N-glycosylation sites (N-glycosites) and intact N-glycopeptides. Serum samples were analyzed using a hydrophilic interaction liquid chromatography (HILIC)-based MS method to perform comprehensive glycoproteomic profiling at both the site-specific glycopeptide and intact N-glycopeptide levels. This approach enabled the simultaneous identification of glycosylation sites and their attached glycan structures, offering high-resolution insights into glycan heterogeneity across glycoproteins. These findings advance our understanding of the molecular mechanisms underlying T2DM&CHD and show the promising value of glycoproteomics for identifying disease-specific biomarkers.