Carbohydrate microarrays provide access to high through-put analysis of protein–carbohydrate interactions. Herein we demonstrate the use of SPR imaging (SPRi) of glycoarrays to assess the ligand specificity of the reputedly galactose-specific plant lectin RCA120 (Ricinus communis agglutinin 120), a surrogate for the bioterrorism agent ricin. Glycoarray studies identified RCA120 ligands based on galactose substituted at the 6-position with sialic acid. These observations, which were confirmed by saturation transfer difference (STD) NMR spectroscopy studies, inspired the synthesis of non-natural 6-substituted galactose derivatives, which were shown to have ∼3–4 fold enhanced binding to RCA120 with respect to the unsubstituted compound. These novel unnatural galactosides, which are chemically and biologically more robust than their natural glycan counterparts, represent new potential ligands for the development of carbohydrate-based ricin sensors.