Introduction: Membranous glomerulonephritis (MGN), an autoimmune kidney disease, often progresses to renal failure. Current treatments have significant side effects, highlighting the need for alternatives. Acanthopanacis Cortex (AC, Wujiapi), a Traditional Chinese Medicine, exhibits anti-inflammatory and antioxidant properties, but its mechanisms in MGN are unclear. Using network pharmacology and cell experiments, this study investigates AC’s therapeutic potential in MGN. Methods: AC constituents were sourced from literature and TCMSP, with targets predicted using PharmMapper and SwissTargetPrediction (OB ≥ 30 %, DL ≥ 0.18) and standardized via UniProt. MGN-related targets from DisGeNET and CTD were analyzed using Venn diagrams, Cytoscape networks, and STRING PPI, with enrichment via Metascape. Core compounds and targets were validated by molecular docking with AutoDock and PDB. RAW264.7 cells treated with AC, sesamin, and LPS were assessed for viability (MTT), NO production (Griess), COX-2/iNOS (Western blot), and ROS (DCFH-DA staining). Results: 15 bioactive compounds from AC, targeting 409 genes (109 linked to MGN), were analyzed, revealing key pathways via PPI, KEGG, and GO. Molecular docking confirmed strong compound-protein interactions. AC and sesamin (≤50 μg/mL/μM) reduced NO, inhibited COX-2/iNOS, and alleviated oxidative stress in LPS induced inflammation without toxicity. Discussions: TCM extracts like Tripterygium wilfordii, Astragalus membranaceus, and Panax notoginseng exhibit anti inflammatory and kidney-protective effects, particularly in minimal change nephrotic syndrome (MGN). AC, derived from P. notoginseng, shows therapeutic promise in MGN models. Using network pharmacology, this study identified five key components in AC, including (-)-kaur-16-en-19-oic acid, acanthoic acid, sesamin, and β-sitosterol, which modulate pathways like PI3K-Akt, JAK-STAT, and MAPK, suggesting mechanisms for MGN treatment. Experimental validation confirmed AC’s anti-inflammatory effects in LPS-stimulated cells, reducing NO release, oxidative stress, and cytokines, supporting its efficacy in MGN.