In recent years, Polypodium leucotomos has emerged with a great interest for having medicinal and therapeutic potential. It is producing very promising results due to the presence of antioxidant and photoprotective properties. Electronic libraries and databases, including Scopus, PubMed, Google Scholar, Science Direct, and Web of Science were searched to identify relevant studies; 79 publications contributed to this review regarding Polypodium leucotomos botanical aspects, chemical composition, antioxidant and photoprotective activity. It is used in complementary and alternative therapies with various pharmaceutical dosage forms (systemic or topical). Thanks to the composition of phytochemical constituents present in the leaves and rhizomes which confer antioxidant and photoprotective activity that has clinical therapeutic potential to be used as systemic and topical sunscreen of natural origin for the prevention of different types of skin diseases caused by harmful ultraviolet A and ultraviolet B radiations. However, more studies are needed in the future to test the ability and enhance the capacity of sunscreen and sunblock in cosmetic formulations. To conclude, it is recommended to carry out scientific studies based on different analytical methods to evaluate the phytoconstituents potential and to develop stable pharmaceutical formulations according to the skin phototype.