Inflammation is the root cause of a number of degenerative diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), asthma, multiple sclerosis (MS), and atherosclerosis. Although drugs and biologic agents are effective in inhibiting the inflammatory process, their long-term usage involves an increased risk of infections and the possibility of developing malignancies. Polyunsaturated fatty acids (PUFAs) and their metabolites have revealed their crucial role in the pathophysiologic processes of inflammation. Altering fatty acid types and their composition in phospholipids of immune cells through diet supplements has proven beneficial in controlling the clinical outcomes of inflammatory diseases. The types of fatty acids being esterified in membrane phospholipids provide a characteristic fatty acid composition of the phospholipids, which can dictate the characteristics of the inflammatory response depending on the types of metabolites of polyunsaturated fatty acids formed through the lipoxygenase and cyclooxygenase pathways, either promoting or inhibiting the inflammatory process, by controlling intracellular signaling pathways. Therefore, dietary management through supplementation of omega-3 fatty acids is sought as an alternative approach for the clinical management of inflammatory diseases.