As a class of macrocyclic host with excellent water solubility, low biotoxicity and high charge density, multicharged cyclodextrins have been extensively studied because they can interact with organic/inorganic/biological molecules through multiple synergistic forces such as the hydrophobic cavities and electrostatic interactions to construct the smart supramolecular assemblies with stable topology, functional diversity and stimulus responsiveness. The latest research progress of pH-, photo-, enzyme-, redox-, magnetic-and multi-stimulus responsive smart supramolecular assemblies, which are constructed by typical positively/negatively charged and amphiphilic multi-charged cyclodextrins including their application in the fields of drug delivery, controlled release and sensory detection is introduced, and the challenges and future developments of multi-charged cyclodextrin smart supramolecular assemblies are discussed.