Over the last few decades, nutraceuticals have become a popular research topic as the focus of nutrition science has shifted from providing basic nutrition to promoting health and ensuring well-being. There is great interest in nutraceuticals for reasons such as an aging population and increasing global awareness of health promotion or disease prevention. Polyunsaturated fatty acids are one of the nutrients with remarkable nutraceutical potential. Many polyunsaturated fatty acid metabolites, especially essential fatty acids and eicosanoids synthesized from eicosapentaenoic acid or arachidonic acid play an active role in the nutraceutical properties attributed to polyunsaturated fatty acids. Polyunsaturated fatty acids have nutraceutical roles in diseases including cardiovascular diseases, type-2 diabetes, non-alcoholic fatty liver disease, neurodegeneration, and cancer, through several biochemical pathways, especially antioxidant and anti-inflammatory effects. In this chapter, the functional aspects of polyunsaturated fatty acids as nutraceuticals and the mechanisms on which they are based are summarized according to the current scientific literature.