Developing a successful way to solubilize C60 in water is a longstanding, critical, and challenging issue in nanotechnology, biological, and medicine applications because of the great potential of fullerene derivatives in anti-viral therapy. In the current study, an efficient strategy for the preparing of water-soluble C60 at room temperature has been developed by complexion of C60 with hyperbranched polyglycerol linked to the β-cyclodextrin core (β-CD-g-HPG). The interactions between C60 and β-CD-g-HPG were investigated using a range of analytical techniques such as FTIR, NMR, UV–vis spectroscopy as well as visual techniques including SEM and AFM images. The particle size for a 1:2 (C60: β-CD-g-HPG) complex was also determined to be monodisperse ∼60nm from DLS, and it was appropriately matched with the size obtained from SEM pictures. The results show our synthesized hybrid nanomaterials will hopefully find interesting applications in biomedicine.