Elevated blood concentrations of homocysteine, B vitamins deficiencies and oxidative stress are etiological factors for many human chronic diseases, yet the etiologic relationship of hyperhomocysteinemia to these disorders remains poorly understood. Clinical trials continue to support the notion that hyperhomocysteinemia is involved in the pathogenesis of oxidative stress and its associated impairment of cellular redox status. Antioxidants, phytochemicals, and bioactive agents are thought to be associated with the reduction of oxidative stress and reducing risk of chronic diseases, yet their role in preventing hyperhomocysteinemia-mediated oxidative stress has not been well covered in the literature.