our study employed a combined proteomic and glycoproteomic approach to investigate the role of protein glycosylation in lipopolysaccharide (LPS)-induced neuroinflammation models. Bioinformatics analysis of the proteomic and glycoproteomic data further emphasized a strong connection between our observed changes and pathways implicated in glycosylation and neuroinflammation. Our findings revealed an overall increase in protein glycosylation levels during neuroinflammatory processes. Crucially, we demonstrated that the pan-glycosylation inhibitor NGI-1 effectively suppressed the inflammatory response in BV2 microglia cells. Building on these findings and leveraging the proteomic and glycoproteomic data from LPS-induced models, we subsequently screened Tanshinone IIA (STS), a bioactive component of Salvia miltiorrhiza (Danshen), identifying it as a potent therapeutic candidate for neuroinflammatory disorders. Tanshinone IIA effectively attenuated aberrant protein glycosylation by reducing glycan occupancy. Mechanistically, this modulatory effect likely involves influencing UDP-GlcNAc levels within the glycosylation biosynthesis pathway and impacting N-acetylaspartate metabolism, thereby disrupting aberrant protein glycosylation and consequently alleviating the inflammatory response. Collectively, our findings offer novel insights into the therapeutic potential of targeting glycosylation modifications in neuroinflammation.