We aimed to investigate the target and signal pathway of Smilacis Glabrae Rhixoma (SGR) in the treatment of myasthenia gravis (MG) based on network pharmacology, and to explore its potential molecular mechanism. The main active components of SGR were searched in the pharmacology database of traditional Chinese medicine systems, and analysis platform. The related targets of SGR were obtained by Genecards, connective tissue disease, therapeutic target database, Drugbank, and Online Mendelian Inheritance in Man database. Moreover, the target information was corrected through UniProtKB and also, this data integrated to draw the “Ingredients-targets” network of SGR. Protein interaction analysis was performed in data platform, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways as well as enrichment analysis on disease-drug target was carried out through metascape online platform. A total of 15 active components were collected from SGR, which correspond to 159 targets; There were 1758 MG-related targets; there are 81 targets related to both drug components and diseases, including 12 key targets. In GO bioaccumulation analysis, 1933 GO items were gathered, which were mainly related to the metabolism of active oxygen species and the active factors of postsynaptic neurotransmitter receptor. According to KEGG analysis, SGR may play a role in the treatment of MG through phosphatidylinositol-3-kinase–protein kinase B signaling pathway, T-cell receptor, cAMP, tumor necrosis factor (TNF), and interleukin-17 (IL-17) signaling pathway, Th17 cell differentiation, endocrine resistance, hepatitis, and some cancer pathways. This study shows that SGR mainly treat myasthenia gravis through the regulation of TNF, MAPK1, JUN, TP53 and other targets, T-cell receptor, TNF, and IL-17 signaling pathway, Th17 cell differentiation and other pathways, which reflects the characteristics of multicomponent, multitarget, and multichannel of traditional Chinese medicine, and providing a certain pharmacological basis for the follow-up study.