In recent times, a great number of plants have been studied in order to identify new components with nutraceutical properties, among which are polyphenols. Dietary polyphenols represent a large group of bioactive molecules widely found in the food of plant origin and they have been found able to prevent the onset and progression of degenerative diseases, and to reduce and control their symptoms. These health protective effects have been mainly related to their antioxidant and anti-inflammatory properties. However, it must be considered that the application of isolated polyphenols as nutraceuticals is quite limited due to their poor systemic distribution and relative bioavailability. The present review highlights the potential effect of dietary intervention with polyphenol-rich food and plant extracts in patients with cancer, diabetes and neurodegenerative, autoimmune, cardiovascular and ophthalmic diseases, as well as the possible molecular mechanisms of action suggested in numerous studies with animal models.