This study investigates, for the first time, the ability of calixarene ligands to interact with G-quadruplex (GQ) DNA assemblies, which play a critical role in many biological processes, including gene expression regulation, telomere maintenance, and the surveillance of genome stability and DNA repair mechanisms. Specifically, the interaction between two calix[4]arene compounds, featuring cationic or zwitterionic functional groups on their upper rim, and the parallel tetramolecular (TG