Rationale:UV light deeply penetrates the dermis, leading to inflammation and cell death with prolonged exposure. This is a major contributor to skin photoaging. In the pharmaceutical field, fibroblast growth factors (FGFs) have gained popularity for enhancing skin quality as they facilitate tissue remodeling and re-epithelization. Nonetheless, their effectiveness is significantly hindered by limited absorption.Methods:We have successfully created a dissolving microneedle (MN) patch that contains hyaluronic acid (HA) loaded with FGF-2 and FGF-21. This patch aims to improve the therapeutic efficiency of these growth factors while providing a simple administration method. We determined the performance of this patch in an animal model of skin photoaging.Results:The FGF-2/FGF-21-loaded MN (FGF-2/FGF-21 MN) patch demonstrated a consistent structure and suitable mechanical properties, allowing for easy insertion and penetration into mouse skin. Within 10 minutes of application, the patch released approximately 38.50 ± 13.38% of the loaded drug. Notably, the FGF-2/FGF-21 MNs exhibited significant improvements in UV-induced acute skin inflammation and reduced mouse skin wrinkles within a span of two weeks. Furthermore, the positive effects continued to enhance over a four-week treatment period.Conclusion:The proposed HA-based peelable MN patch provides an efficient approach for transdermal drug delivery, providing a promising method for improved therapeutic outcomes.