Nigella Sativa (NS), Thymoquinone (TQ), and Epigallocatechin-3-Gallate (EGCG) are phytochemicals that might have antioxidant protective potentials on the hamster cheek pouch epithelium (HCPE). We aimed at evaluating and comparing the potential therapeutic outcomes of these 3 phytochemicals by analysis of peripheral White Blood Cell (WBCs) counts. NS whole oil, TQ, and EGCG were administered before, with, or after 7,12-Dimethylbenza[A]Anthracene (DMBA) painting the hamster's left cheek pouch. Before sacrificing each animal, 2 ml of blood was withdrawn into a fine heparin-containing tube to estimate the total WBCs, lymphocytes, MID cells, and granulocytes counts by an automatic count system. All cheek pouches were surgically excised and examined with a light microscope. The three phytochemicals showed different levels of protection against DMBA carcinogenic activity, more specifically, TQ and NS had higher therapeutic potential and might be used for treatment and/or preventive management of oral cancer in the future. However, further investigations are required to address the mechanism of action and feasibility of the clinical application of each phytochemical.