Cancer is a multistage process where each stage involves different molecular, biochemical and cellular events all of which, however, contribute to malignant transformation. Over the last years, substantial scientific evidence has promoted the hypothesis that ROS-induced cellular damage underlies key steps during development of the malignant phenotype including evasion of apoptosis, limitless proliferation, angiogenesis, tissue invasion and metastasis, etc. On the other hand, natural products hold great promise as anti-cancer compounds in preventing against carcinogenesis both in vitro and in vivo. Throughout this article, we aim to review the evidence as to how some of these natural products exert their chemopreventive effects in human carcinogenesis. For this reason, we have placed particular emphasis on oral cancer where significant efforts have been made in alternative therapeutic strategies such as the use of plant-derived natural products. This is of paramount importance given the disease’s high morbidity and mortality rates across the world and specifically in the geographic regions of India and South-East Asia where its incidence is increasing.