A multi-component nanosystem based on graphene and comprising individual cyclodextrins at its surface is assembled, creating hybrid structures enabling new and important functionalities: optical imaging, drug storage, and cell targeting for medical diagnosis and treatment. These nanohybrids are part of a universal system of interchangeable units, capable of mutilple functionalities. The surface components, made of individual β-cyclodextrin molecules, are the “hosts” for functional units, which may be used as imaging agents, for anti-cancer drug delivery, and as tumor-specific ligands. Specifically, individual β-cyclodextrin (β-CD), with a known capability to host various molecules, is considered a module unit that is assembled onto graphene nanosheet (GNS). The cyclodextrin-functionalized graphene nanosheet (GNS/β-CD) enables “host–guest” chemistry between the nanohybrid and functional “payloads”. The structure, composition, and morphology of the graphene nanosheet hybrid have been investigated. The nanohybrid, GNS/β-CD, is highly dispersive in various physiological solutions, reflecting the high biostability of cyclodextrin. Regarding the host capability, the nanohybrid is fully capable of selectively accommodating various biological and functional agents in a controlled fashion, including the antivirus drug amantadine, fluorescent dye [5(6)-carboxyfluorescein], and Arg-Gly-Asp (RGD) peptide-targeting ligands assisted by an adamantine linker. The loading ratio of 5(6)-carboxyfluorescein is as high as 110% with a drug concentration of 0.45 mg mL−1. The cyclic RGD-functionalized nanohybrid exhibits remarkable targeting for HeLa cells.