Ascorbic acid or Vitamin C is a potent dietary antioxidant with a double faced character, in that it exhibits a pro-oxidant activity arising from its routine antioxidant property that generates reactive free radicals, which induce cytotoxic effects at pharmacologic concentrations. A systematic review of this effect of ascorbic acid in the oral tumours and normal oral tissues would clearly elucidate the merits or demerits of employing vitamin C in treating the same. The aim of our systematic review is to critically review the studies reported in literature that have studied the pro-oxidant activity of ascorbic acid as a therapeutic option for treatment of oral neoplasms and its effects on normal oral cells. Articles were searched in PUBMED, MEDLINE using appropriate key words like "ascorbic acid", "pro-oxidant activity", "treatment", "oral neoplasms". Hand search of Journals was also performed. Articles were reviewed and analysed. The search strategy included 17 potentially relevant articles for review of which, 12 were in vitro studies; 3 were in vivo animal studies; 1 was in vivo human study and 1 was ex vivo human study. The optimum concentration of ascorbic acid used to produce potential pro-oxidant associated cytotoxic effects was found to be 3-5mM in vitro, 0.88-5mM in vivo animals, 0.5-2mM ex vivo in humans, and the corresponding effects are induction of apoptosis (caspase activation), necrosis, free radical formation, H2O2 generation, and DNA fragmentation. In contrast, the same pro-oxidant concentrations had no effect on the normal cells. The results of our systematic review show that the pro-oxidant activity of pharmacologic ascorbic acid is a part of its dose-dependent bimodal activity and is a result of the proposed Fenton mechanism. In vitro, animal and ex vivo studies of pharmacologic ascorbic acid (AA) have yielded meritorious results proving vitamin C as an effective cytotoxic agent against oral neoplastic cells with potentially no harming effects on normal cells. However, a shortage of clinical trials and in vivo human studies pertaining to evaluation of anti-tumour activity of vitamin C in tumours of oral cavity remains a lacuna in concluding ascorbic acid as a beneficial therapeutic option in treatment of oral neoplasms. Copyright © 2013 Elsevier Ltd. All rights reserved.