This study aimed to investigate the chemical constituents and mechanism of alleviating HUA of Polygonatum sibiricum extract (PSE) based on ultra-high performance liquid chromatography-electrospray ionizationtriple quadrupole/linear ion trap mass spectrometry (UPLC-ESI-QTRAP-MS/MS) system, network pharmacology and molecular docking techniques. Using the xanthine oxidase (XOD) inhibitory activity and extraction yield as evaluation indexes, the extraction process of Polygonatum sibiricum was optimized through single-factor experiments. UPLC-ESI-QTRAP-MS/MS was employed to characterize the chemical composition of PSE. The bioactive constituents were screened based on pharmacokinetic methods, targets of hyperuricemia were obtained from GeneCards database. A "protein-protein" interaction network was constructed using the STRING database, from which key targets were identified. The enrichment analysis of GO terms and KEGG pathways were conducted using DAVID database. A "drug-component-target-pathway-disease" network was constructed using Cytoscape to identify core components. Molecular docking was further employed to validate the binding affinity between core components and key targets. The optimal extraction conditions for PSE were extraction time of 60 min; solid-liquid ratio of 1∶25 (g/mL), and extraction temperature of 60 ℃. Under these conditions, the extraction yield of PSE reached 59.53% ± 0.44%, and IC₅₀ of XOD inhibitory activity was 24.57 mg/mL, and exhibited satisfactory antioxidant activity. The 39 bioactive constituents and 125 key targets were filtered. These bioactive constituents could ameliorate hyperuricemia by fluid shear stress and atherosclerosis (FSS-AS), advanced glycation end products-receptor for advanced glycation end products (AGE–RAGE) signaling pathway, the tumor necrosis factor (TNF) signaling pathway, and interleukin-17 (IL-17) signaling pathway. The molecular docking results demonstrated favorable binding interactions, confirming the strong molecular binding activity. In conclusion, the optimization of the PSE extraction process enhanced the retention and utilization of XOD-inhibitory constituents from Polygonatum sibiricum. The mechanism underlying its hypouricemic effect may involve the modulation of multiple core targets—such as those in FSS-AS, AGE-RAGE, TNF, and IL-17 signaling pathways—by key compounds including diosgenin, quercetin, and alpinum isoflavone. This multi-component, multi-target, and multi-pathway approach suggests that PSE has the potential to ameliorate hyperuricemia. The study provides valuable insights for the development of Polygonatum sibiricum-based products and offers new strategies for the clinical management of hyperuricemia.