There is growing evidence that a large proportion of upper digestive tract tumors are ascribable to heavy alcohol drinking and tobacco consumption. The cancer-promoting action of ethanol is mediated by acetaldehyde, its first metabolite, also derived from the bacterial oxidation of alcohol by the oral microflora, classified by the International Agency for the Research on Cancer as a carcinogen. Acetaldehyde is also one of the major components of tobacco smoke. These findings suggest two different strategies to decrease the risk of alcohol-related oral cancers: the reduction of the levels of alcohol-derived acetaldehyde in saliva and the reduction of oral bacterial flora. Therefore, the aim of our study was to develop and characterize some buccal tablet formulations containing both 20 mg L-cysteine hydrochloride (able to chemically neutralize acetaldehyde) and 10 mg chlorhexidine diacetate (well-known antiseptic compound active against a large spectrum of oral microbes). One of these formulations, chosen on the basis of its favourable delivery kinetics of the active principles, was demonstrated to be able to reduce acetaldehyde concentration in an in vitro system and to lower its salivary levels in volunteers after ethanol contact. Our findings support the hypothesis that the application of buccal devices containing cysteine and chlorhexidine could reduce salivary acetaldehyde levels and thus the incidence of upper gastrointestinal cancer in drinkers and smokers.