Dietary proteins metabolism involves the production of homocysteine which result from methionine as a sulfur-containing amino acid. Elevated levels of plasma homocysteine are associated with high risk of cardiovascular diseases. However, Previous studies indicate that plasma homocysteine can be used as a tumor marker and can be considered as a risk factor for cancer. The levels of homocysteine in the plasma is highly controlled by diet and several strategies were suggested for lowering plasma homocysteine. In this chapter, homocysteine biosynthesis and metabolism were explained. Diseases associated with hyperhomocysteinemia were discussed with special emphasis on cancer. Various natural products and dietary interventions were evaluated for their anticancer effects through lowering plasma homocysteine. This chapter will provide a solid ground for researchers to understand the link between hyperhomocysteinemia and cancer and the possible role of diet and natural product in lowering plasma homocysteine.