To explore the anti-inflammatory material basis and mechanism of Alismatis Rhizoma, UPLC was employed to establish fingerprints of different batches of this herb. An inflammation model was established with xylene-induced ear swelling in mice, using the inhibition rate of ear swelling, serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) as pharmacological evaluation indices. Grey relational analysis and partial least squares discriminant analysis were employed to analyze the spectrum-effect relationship. Potential anti-inflammatory components of Alismatis Rhizoma screened through spectrum-effect relationships were selected as the research subjects. The component targets were collected from TCMSP, PubChem, and SwissTargetPrediction databases. Simultaneously, disease targets of anti-inflammatory were acquired from GeneCards and OMIM databases, and the intersection targets were identified using Venny. A protein-protein interaction network was constructed with String database and Cytoscape 3.9.0 to screen core targets. GO and KEGG enrichment analyses were performed on the intersection targets. A herb-component-target-pathway network was established using Cytoscape 3.9.0. Molecular docking between potential active components and core targets was conducted with AutoDock Vina to identify the potential anti-inflammatory material basis of Alismatis Rhizoma. Fourteen common peaks were characterized in UPLC fingerprints across eight batches of Alismatis Rhizoma, with seven chemical components being structurally identified. The alcoholic extracts from all batches significantly suppressed mouse ear edema (P < 0.05) and decreased serum levels of both IL-6 and TNF-α (P < 0.05). Spectrum-effect correlation analysis revealed seven candidate anti-inflammatory constituents: alismoxide, alisol C, 23-acetyl alisol C, alisol F, alisol B, 23-acetyl alisol B, and 11-deoxyalisol B. Network pharmacological analysis identified 284 overlapping targets, including five pivotal targets. GO and KEGG enrichment analyses yielded 961 functional terms and 168 signaling pathways, respectively. Molecular docking simulations indicated that the primary pharmacodynamic components (alisol C, alisol F, and alismoxide) exhibited strong binding affinities with key targets: phosphatidylinositol-3-kinase catalytic subunit beta (PIK3CB), phosphatidylinositol 3-kinase catalytic subunit delta (PIK3CD), and heat shock protein 90-alpha family class A member 1 (HSP90AA1).