The construction of smart nanomaterials from host macrocycles that are responsive to specific stimuli has gained significant attention in recent years. The application of pillar[n]arenes has been of particular interest given their ease of functionalization and tunability of the intrinsic cavity electronic properties that allows them to encapsulate a great variety of guests and complex with metal ions with high selectivity via noncovalent interactions, endowing them with captivating properties and functions. Herein, we present the most recent advances in the design and functionalization of pillar[n]arene-based smart nanomaterials, and their applications for sensing, catalysis, drug delivery, and artificial transmembrane channels.