© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim A glyco-array platform has been developed, in which glycans are attached to plasmonic nanoparticles through strain-promoted azide-alkyne cycloaddition. Glycan–protein binding events can then be detected in a label-free manner employing surface-enhanced Raman spectroscopy (SERS). As proof of concept, we have analyzed the binding of Gal1, Gal3, and influenza hemagglutinins (HAs) to various glycans and demonstrated that binding partners can be identified with high confidence. The attraction of SERS for optical sensing is that it can provide unique spectral signatures for glycan–protein complexes, confirm identity through statistical validation, and minimizes false positive results common to indirect methods. Furthermore, SERS is very sensitive and has multiplexing capabilities thereby allowing the simultaneous detection of multiple analytes.