This thesis explores the role of N-glycosylation in human diseases by examining both serum and human immunoglobulin G (IgG) N-glycosylation. By leveraging developments in glycoscience and glycoanalytical technologies, it investigates how N-glycosylation contributes to disease biology in two contrasting clinical cohorts. Chapters 2 and 3 present disease focused investigations of total serum and IgG N-glycosylation. Chapter 2 examines juvenile Nephropathic Cystinosis (NC), a lysosomal storage disorder caused by cystinosin lysosomal human gene CTNS mutations. Using HILIC-UPLC profiling in a double blind cohort, modest predictive power was observed when applying dimensionality reduction to glycan datasets. However, unblinded analysis revealed significant alterations in serum N-glycosylation, particularly reduced sialylation, providing the first evidence of systemic glycomic dysregulation in NC. These findings suggest broader perturbation of the N-glycosylation pathway and the same study highlights the importance of age stratification in paediatric glycomic studies. Chapter 3 extends this framework to decompensated Liver Cirrhosis, characterising paired serum and IgG glycomes across mixed aetiologies. Profound remodelling was observed, with serum glycosylation shifting toward less complex, agalactosylated (lacking terminal galactose) and asialylated (lacking terminal sialic acids) structures, and IgG exhibiting a pro-inflammatory signature marked by increased agalactosylation and bisected glycans. Importantly, multiple glycomic traits correlated with Model for End stage Liver Disease-Na (MELD-Na) scores, demonstrating that N-glycosylation progressively deteriorates with worsening organ failure and provides biological resolution beyond conventional clinical metrics. The thesis moves beyond disease progression analysis to establish a structured glycoengineering workflow focused on controlled Fc N-glycan remodelling. A chemoenzymatic strategy was developed to redefine the heterogeneous glycosylation landscape of polyclonal human IgG through the application of linkage-specific exoglycosidases and targeted sialyltransferase-mediated glycan installation. Sequential and modular processing enabled the generation of enriched and simplified glycan motifs, producing defined Fc glycan landscapes from a complex starting pool. Complementary molecular dynamics simulations provided structural insight into Fc conformational states and revealed determinants of glycan accessibility within the CH2 domain. Collectively, this work establishes a practical research and development (R&D) platform for the controlled engineering of motif enriched biotherapeutics. Collectively, this thesis demonstrates that systemic N-glycosylation is measurably altered across distinct disease states and establishes a controlled glycoengineering workflow for antibody modification for therapeutic purposes and structural analysis of IgG glycoproteins.