Supramolecular macrocyclic compounds including cyclodextrin, pillararene, calixarene, and cucurbituril are a family of multifarious hosts capable of selectively binding with guests via their intrinsic cavities. They have been used as ideal functional entities on the surface of inorganic nanoparticles to improve their solubility, stability, and biocompatibility in vivo. Macrocyclic compounds can be attached onto the surface of inorganic nanoparticles via covalent or noncovalent bonds, thus acting as a versatile anchoring point, which allows reversible complexation with small molecules via host-guest recognitions. A variety of functional tags including imaging probes, targeting groups, and therapeutic agents can be introduced for further functionalization of the organic-inorganic hybrid nanoparticles. The macrocycles-based organic-inorganic nanohybrids have shown remarkable properties and significant potential in various biomedical applications thanks to the surface modification of macrocycles. Here, we review the versatile construction of macrocycles-based hybrid nanomaterial platforms and discuss their significant potential in biomedical and related applications.