Docosahexaenoic acid (DHA, C22:6 n-3), an omega-3 polyunsaturated fatty acid, offers several beneficial effects. DHA helps in reducing depression, autoimmune diseases, rheumatoid arthritis, attention deficit hyperactivity syndrome, and cardiovascular diseases. It can stimulate the development of brain and nerve, alleviate lipids metabolism-related disorders, and enhance vision development. However, DHA susceptibility to chemical oxidation, poor water solubility, and unpleasant order could restrict its applications for nutritional and therapeutic purposes. To avoid these drawbacks and enhance its bioavailability, DHA can be encapsulated using an effective delivery system. Several encapsulation methods are recognized, and DHA-loaded nanoparticles have demonstrated numerous benefits. In clinical studies, positive influences on the development of several diseases have been reported, but some assumptions are conflicting and need more exploration, since DHA has a systemic and not a targeted release at the required level. This might cause the applications of nanoparticles that could allow DHA release at the required level and improve its efficiency, thus resulting in a better controlling of several diseases. In the current review, we focused on researches investigating the formulation and development of DHA-loaded nanoparticles using different delivery systems, including low-density lipoprotein, zinc oxide, silver, zein, and resveratrol-stearate. Silver-DHA nanoparticles presented a typical particle size of 24 nm with an incorporation level of 97.67 %, while the entrapment efficiency of zinc oxide-DHA nanoparticles represented 87.3 %. By using zein/Poly (lactic-co-glycolic acid) stabilized nanoparticles, DHA's encapsulation level reached 84.6 %. We have also highlighted the characteristics, functionality and medical implementation of these nanoparticles in the treatment of inflammations, brain disorders, diabetes as well as hepatocellular carcinoma.