Background Many experiments showed that Notopterygii Rhizoma Et Radix (NRR) can resist arrhythmia, but the mechanism of its action has not clear. Here, we investigated the possible mechanisms of NRR by network pharmacology and molecular docking and verified them experimentally. Methods Active componds and targets of NRR were retrieved by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database andAnalysis Platform, SymMap, and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Arrhythmia-related targets were acquired from Comparative Toxicogenomics Database (CTD) and GeneCards databases. Overlapping targets of NRR associated with arrhythmia were acquired via Venn diagram. DAVID was applied for GO and KEGG pathway analyses. Cytoscape software and its plug-in were used for PPI network construction, module division and hub nodes screening. AutoDock Vina and qRT-PCR were carried out for validation. Results The 21 active compounds and 57 targets were obtained. Of these, coumarin was the predominant category including 15 components and 31 targets. The 5 key targets of NRR in treating arrhythmia, and these targets are involved in the apoptotic process, extrinsic apoptotic signaling pathway in absence of ligand, endopeptidase activity involved in apoptotic process by cytochrome c. The main pathways are p53 signaling pathway, Hepatitis B and Apoptosis. The results of molecular docking and qRT-PCR display good effect on hub node regulation in NRR treatment. Conclusion NRR plays an important role in anti-apoptotic mediated by modulating p53 signaling pathway, which may provide insight into future research and clinical applications in arrhythmia therapy.