BACKGROUND: Actinic keratoses (AKs) are chronic, recurrent precancerous lesions primarily induced by long-term sun exposure, commonly found on sun-exposed areas such as the face, neck, hands, forearms, and lower legs. AKs are prevalent, affecting millions worldwide, and pose a significant risk of transforming into invasive squamous cell carcinomas (SCCs). OBJECTIVE: This systematic review aims to update the scientific evidence on the role of oral bioactives, nutraceuticals, or dietary supplements in the treatment of AKs and field cancerization, while evaluating their safety and efficacy profile. METHODS: A review plan was pre-registered in the PROSPERO database (CRD42023485985). Following the PRISMA guidelines, we identified, selected, and included relevant studies. We screened a total of 234 articles, thoroughly reviewed 38 full texts, and ultimately included 21 articles published from 2013 through 2023 for analysis. RESULTS: The selected studies were categorized into 3 groups based on the chemical nature of the supplements: polyphenols (11 studies), vitamins (8 studies), and others (2 studies). The studies included preclinical (9) and clinical (12) studies. Clinical trials have demonstrated the efficacy profile of polyphenolic supplements, such as Polypodium leucotomos extract (PLE) and others in improving skin health and reducing the risk of skin cancers. Preclinical studies highlighted the protective effects of polyphenols against UV-induced damage and neoplastic transformation. Vitamin supplementation studies revealed mixed results, with clear data showing benefits in reducing the risk of precancerous lesions and skin cancers after nicotinamide (NAM) treatment, while others did not demonstrate significant protective effects. CONCLUSIONS: The review confirms the efficacy of polyphenols in preventing and treating AKs and related skin conditions. However, the role of vitamins and other supplements requires further investigation due to inconsistent and/or scarce findings. Future clinical trials should focus on diverse populations at higher risk of skin cancer and explore new ingredients as well as combinations of various ingredients to optimize therapeutic applications.