Quercetin is a bioactive flavonoid widely used as a health supplement. Being sparingly soluble and chemically unstable in aqueous intestinal fluids, quercetin is poorly absorbed orally. This study aimed to investigate the effects of three bcyclodextrins, namely, unsubstituted b-cyclodextrin (b-CD), hydroxypropyl-b-cyclodextrin (HP-b-CD), and sulfobutyl ether b-cyclodextrin (SBE-b-CD) on the chemical stability and water solubility of quercetin, and to elucidate the complexation mechanisms of these b-CDs with quercetin. Quercetin-b-CD complexes in solution were characterized by stability assessment, phase solubility measurements, and 1 H-nuclear magnetic resonance (NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of the b-CDs with quercetin. Solubility enhancements of quercetin obtained with the three b-CDs followed the rank order: SBE-b-CD > HP-b-CD > b-CD. The stability of quercetin at alkaline pHs also showed substantial improvement. NMR spectroscopic analysis suggested that the B-ring, C-ring, and part of the A-ring of quercetin display favorable interaction with the hydrophobic cavity of the b-CDs, which was confirmed by molecular dynamics (MD) simulations using a solvated model of the quercetin-b-CD complex. An inclusion complex model has been established for explaining the observed augmentation of solubility and stability of quercetin in water by b-CDs.