Fullerene derivativesFullerene derivatives (FDs) belong to the carbon nanostructures. In recent years, they have found wide application in many industries, e.g., in the production of nanomaterialsNanomaterials, pharmaceuticals and in the biomedical field. Predictive modelingPredictive modeling plays a key role in optimizing the properties of fullerenes for specific applications by providing insights into their structure–property relationshipQuantitative structure-activity/property relationship and facilitating the virtual screening and design process. Computational techniques were used to identify, from a large library, fullerenes which bind to specific target proteins that fulfil various functions in the organism (initiation of metabolic reactions, DNA replication, response to stimuli, transport of molecules, etc.). In this chapter, we discuss models for predicting the binding affinityBinding affinity of FDs to various proteins. The pharmacological and toxic properties of FDs were the focus of investigation. First, we developed binding affinityBinding affinity prediction models to determine the characteristics that influence binding affinityBinding affinity. Second, our study focuses on the inhibitory activity of FDsInhibitory activity of fds in the context of diabetes. Finally, the aquatic toxicity of FDsAquatic toxicity of fds was investigated using human proteins similar to the aquatic spices in our models as examples. The developed computational models can be very helpful for understanding the properties and exploring the potential applications of fullerenes in various scientific and technological fields.