Glycosylation is an important and prevalent post-translational modification that plays a role in diverse biological functions including protein folding, intracellular signaling, and immune response. Glycosylation occurs when glycan chains become covalently attached to side chains of proteins and leads to increased structural heterogeneity. In response to physiological changes, the structure and distribution of glycans at a particular glycosite (micro-heterogeneity) and the presence or absence of a glycan at a glycosite (macro-heterogeneity) can be altered. The two most common types of protein glycosylation are O-linked glycosylation, which occurs at the oxygen of serine or threonine residues, and N-linked glycosylation, which occurs at the amide nitrogen of the asparagine residue's side chain in the predictable sequence Asparagine-X-Serine/Threonine (NXS or NXT), where X is any amino acid except proline. Because of their biological importance, glycoproteins are a high-value target for structural characterization and quantitation via mass spectrometry-based proteomics, with bottom-up proteomics being the approach used most frequently. Bottom-up proteomics is a powerful tool that can be used for the identification and quantification of many proteins by digesting proteins into peptides prior to analysis by nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, it is difficult to characterize glycosylation with traditional bottom-up proteomics. While non-modified peptides can be easily matched to their resulting MS spectra, the additional and variable mass of glycans results in the omission of glycopeptides in the results of standard database searches. Many proteomic software packages, such as MSFragger and MetaMorpheus, are equipped with glycomodules to enable glycoproteomic analysis; however, enrichment steps are almost always necessary to detect glycopeptides whose signals are suppressed by the high number of non-glycosylated peptides in a given sample. Glycopeptide enrichment methods include lectin affinity chromatography, hydrophilic interaction chromatography, and titanium dioxide chromatography. These methods can be used individually or in combination to improve glycoprotein coverage. While many enrichment strategies have been developed, most reported techniques achieve only moderate efficiency and display significant bias towards particular subsets of glycopeptides. In addition, inclusion of glycan enrichment increases the number of sample handling steps required prior to analysis with a concomitant increase in time.