Glehniae Radix (GR) primarily produced in Laiyang and Chifeng. It is a functional food with therapeutic and health-promoting effects due to its antioxidant and anti-inflammatory properties. However, the current standards only stipulate authentication criteria, without establishing a comprehensive evaluation framework to systematically enhance the quality control of GR. This study aimed to establish a "chemical-mechanism" quality control framework for GR through a three-tiered strategy: "chemical composition analysis - bioactivity quantification - mechanism network validation." Initially, UPLC fingerprints of 14 GR batches were constructed, and their antioxidant and anti-inflammatory activities were evaluated. Multivariate statistical models combined with activity indices were employed to optimize spectrum-effect relationships using a random forest algorithm, predicting bioactive constituents. Network pharmacology, molecular docking, and dynamics simulations were integrated to elucidate multi-component, multi-target, and multi-pathway mechanisms. Chemometric analysis identified Imperatorin as a marker for quantifying differences between Laiyang and Chifeng origins. Pharmacodynamic assays confirmed GR's antioxidant and anti-inflammatory efficacy. Random Forest-optimized spectrum-effect modeling prioritized falcarindiol and panaxynol as bioactive markers. Network pharmacology predicted GR's regulation of EGFR tyrosine kinase inhibitor resistance and ErbB signaling via targets (EGFR, PTGS2, NFKB1). Molecular docking revealed strong binding affinity (e.g., imperatorin-EGFR: -9.046 kcal/mol), and dynamics simulations confirmed complex stability. Thus, imperatorin, falcarindiol, and panaxynol were prioritized as quality markers. This study establishes a data-driven framework linking GR's chemical composition to antioxidant/anti-inflammatory mechanisms, advancing batch consistency control and precision applications in clinical disorders.