This study reports the development of novel chiral sensors based on the self-assembly of perfunctionalized beta-cyclodextrins (beta-CD) on a quartz crystal microbalance transducer for real time chiral recognition. Ten chiral sensors immobilized with mercaptyl perfunctionalized beta-cyclodextrins were found to exhibit promising enantioselectivity in the gas phase. Well-defined sizes of molecular cavities of the modified beta-CDs associated with cooperative weak interactions with the host molecules afforded enhanced chiral discrimination. This study contributes to the realization of novel chiral sensors applicable for real-time recognition and analysis of enantiomeric alcohols and lactates.