To date, nutritional supplements in the forms of vitamin and minerals have not shown preventive effects, other than vitamin A and B-carotene that have significant adverse effects or other systemic health risks that have led to recommendations against use of systemic supplementation. Some investigations also suggest that the consumption of whole grain foods as well as a diet high in fiber intake may also be protective. Studies investigating specific dietary micronutrients in relation to OPC have suggested that vitamin C may be associated with a reduced risk. It is not clear, however, whether these micronutrients are directly responsible for the risk reduction, or whether they are markers for some other responsible factor and the adverse effects seen to date do not allow recommendations for use. Multivitamins have not emerged as protective in terms of OSCC/OPC, and while two case-control studies have suggested that vitamin E supplementation may be protective, it is too early to recommend this supplement to patients. Coffee consumption has been assessed in large population studies, with beneficial effects attributed to plant phenols and antioxidants. Finally, although various potential oral cancer chemopreventive agents have been and are being evaluated for their effectiveness and safety, the use of these agents remains experimental at this time. Although patients and consumers may self-prescribe dietary supplements for prevention of OSCC/OPC, it is up to clinicians to advise patients about the lack of supportive evidence and risks associated with some dietary supplements. Chapter 9 in this book addresses dietary supplementation in greater depth.