Skin photoaging is primarily induced by ultraviolet B (UVB) radiation and characterized by degradation of the extracellular matrix (ECM) and chronic inflammation. This study aimed to investigate the anti-photoaging activity and molecular mechanism of a polysaccharide (P2) from Sargassum fusiforme. In a UVB-induced photoaging model of HaCaT cells, P2 treatment significantly alleviated morphological damage. At the protein level, P2 (0.5 mg/mL) significantly inhibited the secretion of MMP-1, MMP-3, and MMP-9 (with inhibition rates of 46.72%, 53.52%, and 56.48%, respectively), while promoting the secretion of their inhibitor TIMP-1 and the key growth factor TGF-β1. P2 also reduced the levels of pro-inflammatory cytokines IL-6 and TNF-α. At the gene level, P2 upregulated the expression of COL1α1 (up to 5.80-fold compared to the model group) and downregulated the transcription of MMP-1, MMP-3, MMP-9, and inflammatory genes (IL-6, TNF-α). Gene expression analysis revealed that P2 activated the UVB-suppressed TGF-β/SMAD signaling pathway, significantly upregulating the expression of TGF-β1, TβR-Ⅰ, TβR-Ⅱ, and downstream SMAD2/3/4, while inhibiting SMAD7 and downstream effector genes c-JUN/c-FOS. Functional validation confirmed that blockade of this pathway using the inhibitor LY2109761 abolished the pro-collagen synthesis effect of P2 and markedly reduced its inhibitory efficacy on MMPs (e.g., inhibition of MMP-1 decreased from 41.18% to 13.81%). Conversely, in TGF-β1-overexpressing cells, the effects of P2 were further enhanced. In conclusion, polysaccharide P2 from Sargassum fusiforme mitigates skin photoaging by targeting and activating the TGF-β/SMAD signaling pathway, thereby coordinately regulating ECM homeostasis and inflammatory responses. These findings provide a solid theoretical foundation for the development of P2 as a natural anti-photoaging agent.