Insulin resistance is a critical pathophysiological process in the onset and advancement of type 2 diabetes mellitus. It is well-recognized that alterations in the metabolism of lipids and aberrant fat buildup effectively trigger the development of resistance to insulin. Adjusting one’s eating habits and managing weight appropriately are crucial for treating, controlling, and reducing the risk of T2DM because obesity and a lack of physical exercise are the primary factors responsible for the worldwide rise in T2DM. Omega-3 fatty acid is one of the polyunsaturated fatty acids (PUFA) that include long-chain omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, commonly found in fish oils. Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs; 3 and 6 PUFAs) are essential for human health because they serve as metabolic precursors of eicosanoids, a class of signaling molecules that are essential for controlling a body’s inflammation. Since humans are unable to produce any of the omega-3 or omega-6 PUFAs, they both constitute imperative nutritional ingredients. Long-standing concerns about long-chain omega-3 fatty acids’ impact on diabetes management have been supported by experimental investigations that found significant increases in fasting glucose following omega-3 fatty acid supplementation and foods rich in PUFA and omega-3 fatty acid. Cellular explanations to explain the connection between inflammation and IR include mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and oxidative stress. Modifications in the lipid composition of mitochondrial membranes and/or receptor-mediated signaling may be part of the mechanism behind the activation of mitochondrial fusion by fish oil/omega-3 PUFA. The exact molecular processes by which omega-3 PUFAs control mitochondrial activity to defend against IR are still unknown.