Abstract: Cyclodextrins (CDs) are nano-macrocycles composed of saccharidic units. The interest for this class of molecules spans from their use as functional encapsulators to building blocks of more complex aggregates. In this fashion, well-established nanostructures can be rationally planned in aqueous medium, originating different nanomaterials with distinctive biological properties, dependently on physico-chemical features of molecular components and their self-assembly. The aim of this contribution is to review research work dealing with CD nanomaterials realized as follows: i) aggregates of native or pharmaceutical trade CDs, ii) supramolecular self-assemblies based on CD by focussing on photo-responsive nanomaterials as well as mixed systems based on CD and polymers, iii) hard metal nanoparticles whose behaviour becomes soft by capping with CD. Through a critical overview of these issues, the properties of nanostructures in biologically relevant media and their potential application as nanotherapeutics will be highlighted. Moreover, studies on CD nanomaterials biofate upon passive targeting into solid tumors, cell uptake mediated by receptor targeting groups and intracellular trafficking will be discussed.