Thrombus formation in a disrupted endothelium is influenced not only by the platelet redox state and reactive oxygen and nitrogen species but also by the presence of endogenous or exogenous antioxidants. Thrombus formation in the stenotic arteries is triggered predominantly by attenuated shear stress. Superoxide and nitric oxide production, as well as their metabolism, potentially influence platelet activation and thrombosis. Antioxidant supplementation has not been generally associated with better cardiovascular outcome and is often compounded by bleeding and hemorrhagic stroke. Because of recent developments like the human genome project and personalized medicine, an emerging new area of nutrigenomics and nutraceuticals offers a scientific approach of diet-based therapeutics applicable to a plethora of human diseases, including cardiovascular inflammation and thrombosis. Therefore, further mechanistic research using nutragenomics and nutraceuticals in the prevention and management of thrombosis offers great potential and may be effective in limiting the problems associated with antioxidant-based therapeutics. In the present review, we have summarized the effect of dietary antioxidants in the modulation of platelet-mediated thrombosis. In addition, therapeutic opportunities in the area of nutragenomics and nutraceuticals in vascular and nonvascular diseases are also discussed.