Selective enrichment of glycopeptides from complicated biological samples is critical for glycoproteomics to obtain the structure and glycosylation information of glycoproteins using mass spectrometry (MS), which still remains a great challenge. Hydrophilic interaction chromatography (HILIC)-based strategies have been proposed for selective isolation of glycopeptides via the interactions between the glycan of glycopeptides and the matrices. However, the application of these methods is limited by the medium selectivity of HILIC matrices. In this study, hydrophilic metal-organic frameworks (MOFs) were fabricated and used as a HILIC matrix. The cross-linked CD-MOFs (LCD-MOFs) were facilely prepared with γ-cyclodextrin as ligand and possessed nano-sized cubic structure, superior hydrophilicity, and bio-compatibility. The LCD-MOFs performance for the selective enrichment of glycopeptides from the complex biological samples were investigated with a digested mixture of human immunoglobulin G (IgG) that was used as standard samples. In the selectivity assessment, the non-glycopeptides causing ion suppression to the glycopeptides were effectively removed, the signal of glycopeptides were enhanced significantly by LCD-MOFs, and twenty glycopeptides were identified with 67 fmol of IgG digest. In addition, the resulting LCD-MOFs demonstrated the lower detection limit (3.3 fmol) with a satisfactory recovery yield (84-103%) for glycopeptide enrichment from a digest of IgG. Furthermore, a promising protocol was developed for the selective enrichment of glycopeptides from mouse liver, and 344 unique N-glycosylation sites that mapped to 290 different glycoproteins were identified in a single MS run. The results clearly demonstrated that when used in a HILIC matrix, LCD-MOFs have great potential for identifying and enriching low-abundant glycopeptides in complex biological samples.