Background <p>Skin photoaging leads to the deterioration of dermal collagen and overall skin integrity, resulting in visible signs of aging, particularly around the eye. Collagen III plays a pivotal role in maintaining skin elasticity and facilitating proper collagen fibril organization. Messenger RNA (mRNA)-based therapeutics present a novel alternative for addressing these limitations by enabling the localized production of full-length, biologically active proteins.</p> Methods <p>This study evaluates the therapeutic effects of human collagen III (hCOL3A1) mRNA on UVB-induced skin photoaging using in <i>vitro</i> and in <i>vivo</i> models. In <i>vitro</i>, human fibroblasts were used to assess oxidative stress, senescence, apoptosis, proliferation, and migration. In <i>vivo</i>, a UVB-induced murine photoaging model was used to assess skin barrier function, dermal thickness, collagen content, and senescence markers were analyzed post-treatment. Transcriptome analysis was conducted to explore gene expression changes and key pathways involved in photoaging and repair mechanisms.</p> Results <p>Our findings demonstrate that h<i>COL3A1</i> mRNA reduces oxidative stress, senescence, apoptosis and promotes cell proliferation and migration in a photoaging cell model. In a murine photoaging model, h<i>COL3A1</i> mRNA significantly improves skin barrier function, enhances dermal thickness, restores collagen content, improves dermal structure, and reduces cellular senescence markers without inducing systemic toxicity or immunogenicity. Transcriptome analyses reveal that h<i>COL3A1</i> mRNA reverses UVB-induced gene expression changes, reinstating critical signaling pathways for skin homeostasis and fibroblast function.</p> Conclusions <p>These results highlight hCOL3A1 mRNA as a promising therapeutic candidate for skin photoaging and underscore the potential of mRNA-based therapies in dermatology and regenerative medicine.</p>