In recent years, the impact of ultraviolet (UV) radiation on skin photoaging and its underlying mechanisms have garnered increasing attention. Our previous study identified Acein, an angiotensin-converting enzyme 1 (ACE1)-targeting peptidethat ameliorates aging phenotypes and significantly extends lifespan in Caenorhabditis elegans by downregulating C-type lectin domain-containing protein CLEC-126 expression. However, the therapeutic potential of Acein in human skin photoaging and the roles of ACE1 and CLEC4G (C-type lectin domain family 4 member G, the human homolog of CLEC-126) remains unclear. In this study, photoaging models in vitro were established and Acein (1 μM) reduced UV-induced oxidative stress and inflammatory markers, suppressed MMPs expression while effectively mitigating collagen III (COL3) degradation and decreased β-galactosidase accumulation. Additionally, functional assays demonstrated Acein enhanced cell viability and migration while reducing G1 arrest and apoptosis. Mechanistically, UV irradiation upregulated ACE1 and CLEC4G expression, which was reversed by Acein. Further investigations revealed that ACE1- knockdown alleviated UV-induced oxidative stress, inflammation and senescence, whereas CLEC4G- overexpression exacerbated these effects. Co-Immunoprecipitation and molecular docking confirmed the interaction between ACE1 and CLEC4G, with Western blotting assays identifying CLEC4G as a key downstream mediator of ACE1-driven photoaging. Moreover, Acein was found to attenuate photoaging by inhibiting the p38-MAPK and NF-κB p65 pathways. In vivo studies using acute photodamage model and photoaging mice model demonstrated that topical Acein application reduced oxidative stress, inflammation, and collagen degradation while mitigating mitochondrial autophagy. Collectively, these findings suggest that Acein represents a novel candidate compound for protecting human skin against UV-induced photoaging.