This review article stresses the effective role of dietary fish fillet docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on overweight as a risk factor of cardiovascular disease (CVD) via platelet phospholipid modification. Several reports have demonstrated that saturated fat in overweight evokes systemic inflammation and more importantly predisposes it to cardiovascular disorder. Prospective studies have shown that saturated fat is directly proportional to the level of arachidonic acids (AA), precursor of thromboxane in the platelet phospholipid membrane as omega-6 fatty acid in overweight and obese people. Some literature has demonstrated that omega-3 fatty acid from fish fillet ameliorates inflammation, reduces proinflammatory cytokine, inhibits signaling pathway, and regulates the physical composition of inflammatory leukocytes and free radicals (ROS). Yellow stripe scad (YSS) is a local Malaysian fish that has been shown to contain a comparable level of EPA/DHA content as observed in salmon. This review article will focus on the dietary role of fish fillet that will balance the omega-6 fatty acid/omega-3 fatty acid ratio in platelet phospholipid from YSS to manage and prevent healthy overweight/obesity-related risk factor of CVD and to avoid the risk orthodox drug treatment.