The loading of drugs or medicinally active compounds has recently been performed using metal–organic frameworks (MOFs), which are thought to be a new type of porous material in which organic ligands and metal ions can self-assemble to form a network structure. The quercetin (QRC) loading and biofilm application on a cyclodextrin-based metal–organic framework via a solvent diffusion approach is successfully accomplished in the current study. The antibacterial plant flavonoid QRC is loaded onto β-CD-K MOFs to create the composite containing inclusion complexes (ICs) and denoted as QRC:β-CD-K MOFs. The shifting in the chemical shift values of QRC in the MOFs may be the reason for the interaction of QRC with the β-CD-K MOFs. The binding energies and relative contents of MOFs are considerably changed after the formation of QRC:β-CD-K MOFs, suggesting that the interactions took place during the loading of QRC. Confocal laser scanning microscopy (CLSM) showed a reduction in the formation of biofilm. The results of the cell aggregation and hyphal growth are consistent with the antibiofilm activity that is found in the treatment group. Therefore, QRC:β-CD-K MOFs had no effect on the growth of planktonic cells while inhibiting the development of hyphae and biofilm inC. albicansDAY185. This study creates new opportunities for supramolecular β-CD-based MOF development for use in biological research and pharmaceutical production.