Lichens are considered a great bio-resource because they produce large numbers of secondary metabolites with many biological activities; however, they have not been cultivated under artificial conditions to date. As a result, lichen substances from natural sources are limited and have not been widely utilized in commercial applications. Accordingly, interest in lichen-associated fungi, especially endogenic fungi, has increased. Ultraviolet (UV) radiation in sunlight is harmful to human health, resulting in demand for effective UV filtering agents for use in sunscreen. In this study, we purified (3R)-5-hydroxymellein, which has UVA absorption activity, from the secondary metabolites of an endolichenic fungus (ELF000039). The antioxidant properties were then assessed by in vitro tests. The antioxidant activity of (3R)-5-hydroxymellein was high when compared to the recognized antioxidants ascorbic acid (ASA) and butyl hydroxyl anisole (BHA). Moreover, the compound exhibited no cytotoxicity toward mouse melanoma cell lines, B16F1 and B16F10, or the normal cell line, HaCaT. Furthermore, (3R)-5-hydroxymellein recovered the damage caused by UVB irradiation and inhibited melanin synthesis. Taken together, these results suggest that (3R)-5-hydroxymellein could have an interesting and vital profile to go further development as a multifunctional skin UV protectant.