To investigate the potential of serum disease-specific immunoglobulin G (DSIgG) crystallizable fragment (Fc) N-glycosylation as a diagnostic biomarker for the identification of nonproliferative and proliferative diabetic retinopathy (DR).A total of 160 patients were enrolled and categorized into three groups according to clinical diagnosis: non-diabetic retinopathy (NDR, n=47); nonproliferative diabetic retinopathy (NPDR, n=51); and proliferative diabetic retinopathy (PDR, n=62). Gel electrophoresis was performed to separate IgG from morning fasting blood samples and polyaniline magnetic nanomaterials (Fe3O4@PANI) were used to enrich IgG N-glycopeptides from tryptic digestion. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI ToF MS) was used to detect the IgG N-glycopeptides.Nine DSIgG N-glycopeptide ratios were significantly different among NDR, NPDR, and PDR groups. There are six glycopeptide ratios available to classify mild, moderate, and severe NPDR. Moreover, four glycopeptide ratios could identify patients with or without diabetic macular edema (DME). The prediction model exhibited good discriminatory performance in distinguishing patients with DR or NDR (AUC=0.8347), NPDR or PDR (AUC=0.7002), mild/moderate or severe NPDR (AUC=0.8059), and with or without DME (AUC=0.7846).DSIgG Fc N-glycosylation ratios were closely associated with different stages of DR and may be used as potential biomarkers for the early diagnosis of NDR, NPDR, and PDR.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.