This study explored the efficacy of curcumin and resveratrol in maintaining adequate zinc levels to regulate p21 and cyclooxygenase-2 (cox-2) during benzo[a]pyrene (BP)-induced lung carcinogenesis. The mice were segregated into five groups, which included normal control, BP treated, BP plus curcumin treated, BP plus resveratrol treated, and BP plus curcumin plus resveratrol-treated groups. BP treatment resulted in a significant decrease in the zinc levels and protein expression of p21. On the contrary, the enzyme activity of cox-2 showed a significant increase in the BP-treated mice. Interestingly, combined supplementation of curcumin and resveratrol to BP-treated mice resulted in an appreciable improvement in the zinc levels and protein expression of p21. In contrast, synergistic supplementation with phytochemicals resulted in a significant decrease in the enzyme activities of cox-2 in BP-treated mice. This study, therefore, concludes that combined treatment with curcumin and resveratrol maintains adequate zinc levels and regulates inflammation by cox-2 and cell cycle arrest by p21 during lung carcinogenesis in mice.