This review deals with recent progress in the synthesis and evaluation of our telomestatin‐inspired macrocyclic polyoxazoles as G‐quadruplex (G4) ligands. The hexaoxazole derivatives (6OTDs) interact with and stabilize G4‐forming oligonucleotides, depending upon the character of the side chain functional groups. Cationic functional groups are particularly effective due to their secondary interaction with phosphate in the DNA backbone. On the other hand, heptaoxazole derivatives (7OTDs) showed potent G4‐binding and stabilization activity regardless of the functional groups on the side chain. A caged G4 ligand, Y2Nv2‐6OTD (7), and a fluorescent G4 ligand, L1BOD‐7OTD (13), have been synthesized. Synthesis and evaluation of macrocyclic polyoxazoles 6OTDs and 7OTDs as G‐quadruplex (G4) ligands are described. These structures were successfully applied to the development of a caged ligand and a fluorescent probe, respectively.