Supramolecular delivery systems (SDSs) fabricated via molecular assembly, which conveniently allow integration of multiple functions in a single system and structural diversity of systems, are a very active research area due to their enormous potential in biomedical applications, including drug delivery, cell imaging, diagnosis, and release monitoring. Pillararenes, a novel type of macrocyclic molecule, are gaining increasing interest as an important component in the construction of SDSs due to their unique structural and chemical properties. This feature article summarizes pillararene-based SDSs constructed via host-guest interactions via four strategies: (1) supramolecular host-guest complexation; (2) self-assembly of supramolecular amphiphiles; (3) self-assembly of amphiphilic supramolecular polymer conjugates; (4) hybridization with other porous materials, such as inorganic materials and metal-organic frameworks (MOFs). The various SDSs based on pillararenes for the delivery of different cargoes from anti-cancer drugs, fluorescent molecules, siRNAs, and insulin to antibiotics are reviewed. Furthermore, future challenges for advanced SDSs based on pillararenes and their broader applications are outlined.