Glycan-mediated molecular recognition is crucial for life. Various methodologies, including nuclear magnetic resonance (NMR), help elucidate these interactions across different complexity levels, from macroscopic to atomic resolution. NMR is widely used to study glycan binding to lectins in solution, though these interactions are typically weak (mM to μM scale) under diluted conditions. In nature, multivalent presentations enhance affinity, making interactions more promiscuous. Herein, we describe an NMR methodology, from the ligand perspective, to investigate glycan-lectin interactions in environments mimicking native cellular conditions. For lectins primarily found on cell surfaces, saturation transfer difference (STD)-NMR was used to examine interactions. This NMR methodology provides a proof of concept for studying glycan-lectin interactions in biologically relevant environments. The ability to detect glycan recognition events on the cell surface expands our understanding of these essential interactions and their implications for biomedical applications, including cancer immunotherapy.