Abstract Oral squamous cell carcinoma (OSCC) is one of the commonest cancers globally. Prevalence of the disease is high in the third world countries of South-east Asia, specifically tied to inherent abuse of tobacco and areca nuts. The disease manifests as oral potentially malignant disorders, such as OED, OSMF, leukoplakias, etc., that provides avenues for effective control early in the sequence of cancer progression and immune evasion. Focus of our study was to gather insights on the potential of natural, biological molecules to intervene early in the carcinogenesis processes. We present herewith, a review of literature and plausible mechanism of action studies carried out widely in cellular or animal models, that remains to be translated successfully to the clinics. We also, discuss further, how green bio-manufacturing methodologies may hasten the process of bringing these molecules for mitigating oral public health challenges, effectively; in a multidisciplinary approach. Further, human studies in blinded clinical trials, is however warranted to ascertain clinical efficacy and safety. In summary, aloe-emodin stands out among anthraquinones for its enhanced anticancer potency and broader therapeutic applications, making it a valuable compound in both research and clinical settings.