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In winemaking, a large amount of grape pomace is produced that is rich in polyphenolics and highly beneficial for human health, as phenols are useful for skin ultraviolet (UV) protection. In this investigation, we evaluated the safety and clinical efficacy of a sunscreen system containing a grape pomace extract from Vitis vinifera L. as a bioactive ingredient. The recovery of phenolics in the waste was performed by percolation. Nine emulsions were developed using a factorial design and two were evaluated clinically: Formulation E, containing only UV filters (butylmethoxydibenzoyl methane, ethylhexyl methoxycinnamate and ethylhexyl dimethyl PABA), and F, with the extract at 10.0% w/w + UV filters. The antioxidant activity was determined by the DPPH assay and the in vitro efficacy was established by sun protection factor (SPF) measurements (Labsphere UV-2000S). Clinical tests were performed to determine safety (human repeated insult patch test) and to confirm efficacy (photoprotective effectiveness in participants). The results showed a synergistic effect between the sunscreen system and the extract on UVB protection and antioxidant activity. Both samples were considered safe. Formulation F was 20.59% more efficient in protecting skin against UVB radiation, taking approximately 21% more time to induce erythema compared to the extract-free sample.