Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder characterized by impaired glucose regulation and/or insulin resistance. As the global burden of T2DM continues to rise, exploring novel therapeutic avenues has become imperative. Omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have gathered substantial attention for their potential benefits in managing T2DM. This chapter provides a comprehensive clinical perspective on the role of omega-3 fatty acids in T2DM and related metabolic disorders. Clinical trials and observational studies have shown promising outcomes regarding omega-3 supplementation in T2DM management, but still its role is debatable. Omega-3 fatty acids exhibit multiple mechanisms of action, including improved insulin sensitivity, reduced inflammation, and enhanced lipid metabolism, as well as regulating the gut microbiome. These effects translate into better glycemic and lipid control and reduced cardiovascular risk, which are paramount in T2DM management. While omega-3 fatty acids present a compelling adjunctive therapy for T2DM and cardiovascular disease (CVD), more extensive and long-term clinical trials are warranted to establish definitive guidelines.