Abstract：In this study, the protective effects of polyphenols from Coreopsis tinctoria Nutt. against glycation-induced aging damage were investigated. First, response surface methodology (RSM) was employed for the optimization of polyphenol extraction from Coreopsis tinctoria Nutt. (CtNE), and liquid chromatographymass spectrometry (LCMS) was applied for component identification. Second, a glycationmediated aging damage model was established in HaCaT cells using methylglyoxal (MGO), and intervention with CtNE was subsequently performed. The levels of advanced glycation end products (AGEs), senescenceassociated βgalactosidase (SAβGal), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected. Reactive oxygen species (ROS) content, cell cycle distribution, and cell apoptosis were analyzed by flow cytometry. The protein expression levels of nuclear factor erythroid 2related factor 2 (Nrf2) and heme oxygenase1 (HO1) were determined by Western blot assay.The results showed that 28 compounds were identified in the optimized CtNE. Compared with the model group (P < 0.05), AGE levels were reduced by 28.81 %, the positive rate of SAβGal was decreased by 43.97 %, and ROS content was lowered by 61.05 % after CtNE treatment. SOD activity was recovered to 95.75 %, while MDA content was reduced by 42.16 %. The proportion of cells in S phase was increased to 35.50 %. Furthermore, the nuclear protein expression of Nrf2 was increased by 2.21-fold and that of HO-1 by 1.82-fold in the high-dose CtNE group, the Nrf2/HO-1 signaling pathway was upregulated, and glycation-induced aging as well as oxidative stress damage in HaCaT cells were ameliorated.This study was designed to provide a theoretical basis for the application of Coreopsis tinctoria Nutt. in improving skin glycation senescence, and its application and development were further promoted.