Polyphenols are plant-derived secondary metabolites that are synthesized as a defence mechanism. Natural polyphenols have long been utilized for their antioxidant, anti-inflammatory, anticancer, and immunomodulatory properties in the prevention and treatment of various disorders. Consequently, these phytochemicals have the potential to function as therapeutic agents in the prevention and treatment of cancer, cardiovascular diseases, diabetes, obesity, and neurological disorders. The low bioavailability of polyphenolic compounds poses a challenge to their effective use. To enhance the bioavailability of these compounds, many forms of formulations have been created, with nanonization being particularly notable. This chapter provides an overview of the biological capabilities of nanoformulated plant polyphenolic chemicals. Additionally, it provides a concise overview of the potential use of different polyphenols as nanoformulations in the management of cancer, diabetes, obesity, neurological disorders, and cardiovascular diseases. Further research is required to explore the efficacy of nanoencapsulated polyphenols, whether used individually or in combination, in both laboratory settings (in vitro) and living organisms (in vivo).