This study aims to evaluate the ability of resveratrol (RSV) antioxidant to attenuate the oxidative stress condition induced by secondhand exposure of cigarettes and waterpipe smoking using animal model. Forty-eight mice were divided equally into six different groups, and RSV was delivered to certain groups intraperitoneally with a dose of 25 mg/kg/day. The process of smoking exposure was performed using a specialized smoking machine. The experiment duration lasts for six consecutive weeks. Five mu m sections of lung were stained with hematoxylin and eosin for light microscopy, and 70 nm ultrathin sections of lung stained with uranyl acetate and lead citrate were prepared for transmission electron microscopy to observe the cellular ultrastructure. In lung, RSV reduced the deterioration and blebbing of bronchiole epithelium, reduced the inflammation, increased the surface area of alveolar sac, and reduced the thickening of alveolar walls. Also, blood vessels were less congested and less dilated with less diffusion of extravasated blood. Ultrastructural images illustrated that RSV protects the normal structure of alveolar septum, prevents DNA damage and alveolar degeneration, showed less degree of apical membrane blabbing and retained the uniform pattern of mitochondria. In conclusion, RSV has ameliorative effects against the oxidative stress condition induced by secondhand (side stream) exposure of cigarette and waterpipe tobacco smoking.