Abstract Cigarette smoking has been established as a major risk factor for atherosclerosis and also for lung cancer. Nicotine is an active substance present in tobacco. We have analyzed the effect of hesperidin, a bioflavonoid on nicotine induced toxicity. Antioxidant status and expression of MMPs (Matrix metalloproteinases) were analyzed to monitor the protective effect of hesperidin against nicotine toxicity. Our result demonstrated that nicotine significantly up regulates the expression of MMPs and depletes the antioxidant status. On treatment with hesperidin we found the down regulation of expression of MMPs and enhancement in antioxidant status. Hence it could be developed as a drug against tobacco related disease in near future.