Introduction: The objective of our study is to explore the potential active ingredients and activity of Ginseng and Astragalus decoction (GAD) in the treatment of malignant pleural effusion (MPE) by using network pharmacology and molecular docking technologies. Methods: The active ingredients and corresponding targets of Ginseng and Astragalus were extracted from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The relevant targets of malignant pleural effusion (MPE) were searched in the disease databases. Overlapping targets of Ginseng and Astragalus and the corresponding targets of MPE were obtained to define the effective target of GAD for the treatment of MPE. The STRING database was applied to construct a predicted protein-protein interaction network for intersected targets. The Cytoscape software was used to screen key targets with a therapeutic potential. Using the Metascape database, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis on the targets identified in the study. PyMOL and AutoDock Vina were used to molecularly dock the selected key components to their respective key targets for MPE treatment. Results: The core target network revealed 22 main active ingredients, 26 main targets, and 16 signaling pathways in GAD. Molecular docking revealed 6 targets (AKT serine/threonine kinase 1, intercellular adhesion molecule, Jun proto-oncogene, peroxisome proliferator activated receptor gamma, prostaglandin-endoperoxide synthase 2, and tumor necrosis factor) that could partially dock with kaempferol, frutinone A, ginsenoside RH2, formononetin, and quercetin. Conclusions: Several components, targets, and signaling pathways of GAD contribute to the treatment of MPE, which suggests a rationale for further investigation on GAD's active molecule and mechanism of action in the clinical application of MPE.