INTRODUCTION: Oral potentially malignant disorders (OPMDs) describe mucosal disorders with an increased risk of malignant transformation (MT) to oral squamous cell carcinoma (OSCC). Natural products like garlic represent a promising group of chemopreventive agents. Aged garlic extract (AGE) is one of the most commonly used garlic preparations as it contains more stable organosulfur compounds (OSCs); S-allylcysteine (SAC) is the most abundant organosulfur compound in AGE. SAC has been found to retard the growth of chemically induced and transplantable tumors in several animal models. OBJECTIVES: To evaluate the cancer chemopreventive effect of topically applied S-Allylcysteine in the management of oral dysplastic potentially malignant disorders. MATERIALS AND METHODS:10 subjects with oral dysplastic potentially malignant disorders, as proven clinically and histopathologically, were recruited for this study. They received topical S-Allylcysteine for 1 month, and then the lesions were evaluated both clinically and histopathologically after termination of therapy to assess any alterations in the lesions' size, pain score and mucosal dysplasia. RESULTS: S-allylcysteine was well tolerated by all the patients. After termination of the therapeutic phase (after one month), S-Allylcysteine was found to decrease the pain score in all symptomatic patients. The size of the lesions was also decreased although it was not statistically significant; however, histological improvement was remarkable. Complete histological response was observed in four leukoplakia patients and two lichen planus patients where the mild and moderate dysplastic changes showed histologic remission of dysplasia. However, two leukoplakia cases showed progression in the grade of dysplasia from mild to moderate. CONCLUSIONS: Topical application of S-Allylcysteine is beneficial for the management of dysplasia associated with oral potentially malignant disorders.