Abstract: Ultraviolet (UV) exposure accelerates skin aging and increases the risk of skin-related diseases. Amentoflavone (AMF), the major compound isolated from Selaginella tamariscina, exhibits potent antioxidant and anti-inflammatory activities. This study aimed to investigate the therapeutic effects and mechanisms of S. tamariscina extract (STE) and AMF on UVB-induced skin photoaging. In vitro and in vivo photoaging models were established to evaluate the protective effects of STE and AMF. The therapeutic target of AMF was identified using network pharmacology, bioinformatic analysis, and molecular docking. In vitro, STE significantly reduced UVB-induced oxidative stress, inflammation, and apoptosis. In vivo, both STE and AMF effectively mitigated UVB-induced skin injury. Mechanistically, AMF directly interacted with AMP-activated protein kinase (AMPK), thereby promoting autophagy and protecting cells from UVB-induced damage. In conclusion, STE and its active compound AMF alleviate UVB-induced photoaging via activation of the AMPK signaling pathway, supporting their potential use in skin photoaging therapy.