The 1,2,3-triazole scaffold has become very attractive to identify new chemical entities in drug discovery projects. Despite the widespread use of click chemistry to synthesize numerous 123Ts, there are few drugs on the market that incorporate this scaffold as a substructure. To investigate the true potential of 123Ts in protein-ligand interactions, we examined the noncovalent interactions between the 1,2,3-triazole ring and amino acids in protein-ligand cocrystals using a geometrical approach. For this purpose, we constructed a nonredundant database of 220 PDB IDs from available 123T-protein cocrystal structures. Subsequently, using the Protein Ligand Interaction Profiler web platform (PLIP), we determined whether 1,2,3-triazoles primarily act as linkers or if they can be considered interactive scaffolds. We then manually analyzed the geometrical descriptors from 333 interactions between 1,4-disubstituted 123T rings and amino acid residues in proteins. This study demonstrates that 1,2,3-triazoles exhibit diverse preferred interactions with amino acids, which contribute to protein-ligand binding.