Spurred on by recent progress in nanotechnology and precision medicine, smart drug carriers are entering an entirely new era. Smart drug carriers have been widely studied in recent years as a result of their ability to control drug release under different microenvironments (such as pH, redox, and enzyme) in vivo. Host-guest interactions based on cyclodextrins have proven to be an efficient tool for fabricating smart drug carriers. Because of the application of host-guest interactions, many kinds of biological molecules or supramolecular building blocks can combine into an organic whole at the molecular level. In this review, the features, mechanisms of action, and potent applications of biological stimuli-responsive drug carriers based on cyclodextrins are discussed. In addition, some personal perspectives on this field are presented.