Todayâs consumers are increasingly aware of the beneficial effects of n-3 PUFA in preventing, delaying, and intervening various diseases, such as coronary artery disease, hypertension, diabetes, inflammatory and autoimmune disorders, neurodegenerative diseases, depression, and many other ailments. The role of n-3 PUFA on aging and cognitive function is also one of the hot topics in basic research, product development, and clinical applications. For decades, n-3 PUFA, especially EPA and DHA, have been supplied by fish oil and seafood. With the continuous increase of global population, awareness about the health benefits of n-3 PUFA, and socioeconomic improvement worldwide, the supply chain is facing increasing challenges of insufficient production. In this regard, microalgae have been well considered as promising sources of n-3 PUFA oil to mitigate the supply shortages. The use of microalgae to produce n-3 PUFA-rich oils has been explored for over two decades and some species have already been used commercially to produce n-3 PUFA, in particular EPA- and/or DHA-rich oils. In addition to n-3 PUFA, microalgae biomass contains many other high value biomolecules, which can be used in food, dietary supplement, pharmaceutical ingredient, and feedstock. The present review covers the health benefits of n-3 PUFA, EPA, and DHA, with particular attention given to the various approaches attempted in the nutritional interventions using EPA and DHA alone or combined with other nutrients and bioactive compounds towards improved health conditions in people with mild cognitive impairment and Alzheimerâs disease. It also covers the applications of microalgae n-3 PUFA in food and dietary supplement sectors and the economic and environmental sustainability of using microalgae as a platform for n-3 PUFA-rich oil production.