AbstractGalectins are a family of galactoside‐binding proteins involved in various pathophysiological processes, which makes them attractive targets for drug discovery. The derivatization of d‐galactose at C3 and C1 positions has been shown to increase the affinity of synthetic galectin antagonists. In this study, two small libraries of d‐galactose derivatives have been designed and synthesized. The first series involved the development of novel aromatic 3‐azolyl‐3‐deoxy‐d‐galactopyranoses. The second series consisted of epimeric analogs of glyceryl β‐S‐d‐galactopyranosides, which were also derivatized. Binding‐affinity evaluations for galectin‐1 and galectin‐3 have revealed that galactose analogs from both series have potential for further optimization. Notably, a combination of modifications at the C3 position of the galactose ring and on the aglycone has led to the identification of promising galectin inhibitors, specifically the compounds 29R and 32S.