Overexposure to ultraviolet (UV) light is associated with multiple health risks, from sunburn and prematurely aging skin to the development of skin cancers. The ingestion of photoprotective natural compounds through diet or supplementation is one method to increase the skin’s UV-resistance. This study’s primary objective was to determine the cellular photoprotective properties of an ingestible skincare supplement (trade name “Anti-Aging Formula” [AAF]) and compare them to its constituent active ingredients: fish oil-derived omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), borage-derived omega-6 gamma-linolenic acid (GLA), paprika- and marigold-derived carotenoids, zeaxanthin and lutein, respectively, and vitamin D3. AAF, but not the separate individual ingredients, significantly increased the viability of primary human dermal fibroblasts after UVA exposure compared to the vehicle control. AAF and EPA/DHA-containing fish oil demonstrated similar UVB photoprotective properties whereas GLA, the carotenoids, and vitamin D3 had no significant effect. The second objective was to explore possible mechanisms of action of AAF’s photoprotective effects. AAF-treatment increased cellular antioxidant activity and the expression of genes in the glutathione and peroxiredoxin (PRDX)/thioredoxin (TXN) antioxidant pathways, suggesting an antioxidant mechanism of action. It also diminished cellular arachidonic acid (AA) levels and decreased the expression of the downstream pro-inflammatory prostaglandin-endoperoxide synthase 2 (PTGS2) gene, suggesting an anti-inflammatory mechanism of action. In conclusion, AAF is UVA/B photoprotective when applied directly to primary human dermal fibroblasts. In addition, its photoprotective effects are mainly due to its EPA/DHA components and may relate to its cellular antioxidant effects and inhibition of the AA/PTGS2 inflammatory pathway.