Galectins 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.