Abstract: Objective: To analyze the pharmacodynamic material basis and mechanism of Dendrobium nobile in the treatment of nervous system diseases using integrative network pharmacology. Methods: The chemical constituents of Dendrobium nobile were collected from the databases of Si-noMed, China HowNet and Wanfang. The constituents were input into TargetNet database for potential target capture. The obtained target was then imported into CTD database to get related diseases. The gene function and pathway enrichment of the target were analyzed by DAVID database. Component-target network and target-disease network were constructed by Cytoscape software. The relation between the ingredients and targets were validated by AutoDock Vina software. Results: A total of 47 components were collected from Dendrobium nobile, which could act on 88 targets. Nobilin D, Nobliomethylene, decumbic acid B, (+)-dendrolactone, (−)-denobilone A, Nobilin were the main material basis for the treatment of nervous system diseases through multivariate network analysis. The components in Dendrobium nobile mainly acted on these key targets including MIF, ERS2, CYP19A1, ABCG2, TLR9 and DRD5, and further regulate the Sphingolipid signaling pathway, Cocaine addiction and Serotonergic synapse for treating nervous system diseases. Conclusion: This study reveals the multi-component, multi-target and multi-pathway action of Dendrobium nobile, and provides a new basis for further research on the mechanism of Dendrobium nobile in the treatment of nervous system diseases.