Multiple system atrophy (MSA) is a fatal neurodegenerative disease, it causes functional degradation of multiple organs and systems throughout the body. Astragalus membranaceus (AM), a well-known traditional Chinese medicine, has been used to improve muscle wasting-related disorders for a long history. In this study, we used network pharmacology and molecular docking to predict the mechanism underlying AM for the treatment of MSA. We screened the active compounds of AM and its related targets, as well as the target proteins of MSA. We made a Venn diagram to obtain the intersecting targets and then constructed a protein-protein interaction network to find the core targets and build an active ingredient-target network map. After subjecting the intersecting targets to gene ontology and Kyoto encyclopedia of genes and genomes analysis, the binding ability of core compounds and core target proteins were validated by molecular docking. A total of 20 eligible compounds and 274 intersecting targets were obtained. The core components of treatment are quercetin, kaempferol, and isorhamnetin, and the core targets are TP53, RELA, and TNF. The main biological processes are related to cellular responses and regulation. Molecular functions are mainly associated with apoptosis, inflammation, and tumorigenesis. Molecular docking results show good and standard binding abilities. This study illustrates that AM treats MSA through multiple targets and pathways, and provides a reference for subsequent research.