Saliva is the first biological fluid that inhaled cigarette smoke (CS) encounters. CS contains several carcinogens known to initiate and promote tumourigenesis and metastasis. One of the aims of this study was to establish if glutathione peroxidase and gamma-glutamyltranspherase (GGT) could be used as possible markers for evaluating the oral oxidative stress caused by smoking. The effect of CS on free radical generation was investigated using two methods. Using different assays, different antioxidants present in saliva may be evidenced due to the different principles on which they are based. Our results indicate that exposure to CS caused a statistically significant decrease of both salivary glutathione peroxidase (p < 0.01) and salivary GGT (p < 0.01). We also found that exposure to CS caused a statistically significant decrease of salivary total antioxidant status (p < 0.01). Such decreases may have a consistent role in the mechanisms by which the toxic effects of CS initiate oral inflammatory diseases, promote precancerous transformations, and destroy the oral cavity homeostasis. Therefore the evaluation of total antioxidant capacity of saliva is important but it must be done together with the evaluation of salivary specific markers of oxidative stress, such as uric acid, albumin and possibly, GGT.