Chemoprevention of oral cancer involves the use of natural or synthetic substances to halt, delay, or reverse the progression of carcinogenesis in the oral cavity. This preventive strategy is especially crucial for individuals at high risk due to genetic factors, lifestyle choices such as tobacco and alcohol use, or the presence of precancerous lesions. Agents like retinoids, green tea polyphenols, lycopene, carotenoids have shown promise in clinical trials, demonstrating their potential to modulate pathways involved in cell proliferation, apoptosis, and inflammation. By targeting molecular mechanisms that underlie oral carcinogenesis, chemoprevention aims to reduce the incidence and mortality of oral cancer, complementing other preventive measures such as regular screenings and lifestyle modifications.