ABSTRACT Physical blocks (i.e. wearing appropriate clothing), exposure avoidance, and the use of sunscreens are the main methods of photoprotection currently used. However, phytochemical and natural botanical extracts such as polypodium leucotomos, a tropical fern found in Central and South America, demonstrate a strong potential as adjuncts to sunscreen protection. A review of the literature was performed focusing on the photoprotective properties of PL extracts, including antioxidant, immunoregulatory, anti-inflammatory and antitumorigenic effects in the context of sunburn, photodermatoses, chronic skin damage, photoaging, and skin cancer. PL supplementation acts at a molecular and cellular level to enhance endogenous antioxidant systems and inhibit generation of reactive oxygen species, thus decreasing UV-mediated oxidative DNA mutations. PL has also been shown to accelerate removal of UV-induced photoproducts, highlighting its anti-carcinogenic role. By reducing UV-induced inflammatory responses and inhibiting extracellular matrix remodeling, PL demonstrates some protective effects against photoaging and PUVA induced phototoxicity. The use of a systemic protective agent would provide significant advantages such as a more uniform coverage over the total body surface area, regardless of individual factors such as potency of the creams, amount applied, sweating, or bathing. Oral administration of PL extracts and its favorable safety profile could have significant implications in the prevention of skin cancer.