Curcumin is a natural bioactive substance with promising biomedical applications. However, the low solubility and stability of curcumin significantly limit its potential use. The development of nanoformulations of curcumin makes it possible to circumvent the above limitations. Cerium dioxide (CeO 2, NDC) nanoparticles are a promising platform for curcumin binding. They are able to absorb curcumin on their surface, providing increased bioavailability and bioaccumulation. Moreover, NDC have unique enzyme-like properties that can be used for targeted delivery and controlled release of curcumin. Meanwhile, the potential cytotoxicity of such nanoformulations remains poorly understood. In this work, we synthesized the NDC-curcumin nanoconjugate and investigated the effect of excess curcumin on the cytotoxicity of this nanoformulation. Curcumin has been shown to bind to the surface of nanoparticles, forming a sustainable and colloidally stable nanoconjugate. At the same time, excess curcumin formed a separate colloidal nanoscale fraction, which caused the pronounced cytotoxicity of the nanoconjugate in relation to human immortalized keratinocytes (HaCaT), primary mesenchymal stem cells (hMSc) and fibroblasts (HF). In turn, NDC provided an increased biocompatibility of curcumin. Thus, the application of a rational design of curcumin nanoformulations will help to overcome possible limitations of its use in practice and maximize its bioactivity.