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Natural plant oils are commonly used in skincare products for their emollient properties. Plum seed oil is a promising cosmetic ingredient since it represents a sustainable material derived from fruit processing waste, recognized in the CosIng Database for its skin-conditioning function. The aim of this study was to incorporate plum seed oil into a topical emulgel and assess its biophysical effects on the skin. An in vivo study on healthy volunteers evaluated the safety (irritation potential) and long-term efficacy (impact on biophysical skin parameters during 28-day application) of emulgel containing 6% (w/w) plum seed oil as a natural emollient and active ingredient. Results showed that plum seed oil exhibited no irritation potential during a 24-hour safety assessment since transepidermal water loss (TEWL) decreased (p <0.05), and erythema index didn’t change significantly. Results of 28-day efficacy study suggested, potential anti-irritant effects after long-term usage. In addition, pH, skin integrity and skin color were preserved during the study, while skin hydration was increased. To our knowledge, this is the first study to employ non-invasive biophysical methods to assess the influence of plum seed oil in cosmetic formulations. These findings point plum seed oil’s potential as a natural, sustainable, safe and effective raw material for cosmetics.