Research over the last four decades has provided convincing evidence supporting the preventive role of dietary agents including medicinal plants and herbs, against the risk of cancer. We now aim to identify natural phytochemical agents that can protect the normal cells (cytoprotection) from the toxic side–effects following chemotherapy treatment. Specific phytochemicals may exhibit chemopreventive abilities by suppressing key biomolecular signaling events during tumor initiation, promotion and progression. In this review, we summarize data regarding selective phytochemicals including Curcumin, Resveratrol, EGCG, Triptolide, Graviola (A. Muricata), Silymarin, Amygdalin (extract from apricots and peach kernels) and Chrysin, with emphasis on the evidence supporting the chemopreventive efficacy of these compounds in high–risk populations as well as their complex biomolecular mechanisms. Moreover, we will discuss how specific phytochemicals might be able to provide new horizons as chemopreventive agents of normal cells during chemotherapy. Such approach may limit the severe adverse toxic side–effects procedure and impotantly enhancing the quality of life of the patients.