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Background: Sensitive skin is a common condition affecting a significant proportion of the population, and there is a growing demand for effective and safe management. Aim: To evaluate the efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate as an optimal care for facial sensitive skin. Methods: A total of 110 participants (64 in group A and 46 in group B) with facial sensitive skin applied the cream twice daily for 28 days. Group A evaluated their sensitive skin, product efficacy, and product use experience at D0 (15 min), D1, D14, and D28. In group B, skin barrier function‐related indicators were measured at baseline and on D1, D7, D14, and D28. Dermatologists evaluated tolerance for all participants. Results: After 28 days of use, in group A, 100% of participants reported mildness and comfort with product use. Participants demonstrated significant improvements in skin barrier function‐related indicators, including increased stratum corneum moisture content, reduced erythema index, elevated sebum content, decreased trans‐epidermal water loss, and diminished skin redness parameter a* value (all p < 0.05). Dermatologist evaluations revealed excellent tolerance among all participants. Conclusion: The panthenol‐enriched cream with prebiotics and probiotic lysate exhibited substantial clinical efficacy in ameliorating facial sensitive skin conditions, coupled with a high safety profile. [ABSTRACT FROM AUTHOR]