Objective. To explore the mechanism of Shaoyao Gancao decoction (SGD) in treatment of alopecia areata (AA) by network pharmacology and animal experiments. Methods Based on the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), the components and targets of SGD were determined. Then, the related targets of AA were retrieved from DrugBank, GeneCards, OMIM, and DisGeNET databases. The intersection of drug targets and disease targets was determined, and the key targets of the protein-protein interaction network were obtained with the String database. Gene Ontology (GO) biological process enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of potential key targets were carried out using the DAVID database using AutoDock for molecular docking verification. Finally, the key pathway was validated by animal experiments. Results. A total of 102 active components, 212 predicted targets, and 812 AA disease-related targets were obtained. Topological analysis yielded 45 key targets of SGD in the treatment of AA, including IL-6, PTGS2, TNF, VEGFA, CCL2, IL-1B, CXCL8, CASP3, MPO, and IL-10. There were 324 GO entries obtained through GO biological process enrichment analysis, and 20 pathways were obtained through KEGG pathway enrichment analysis, involving the PI3K-Akt signaling pathway, osteoclast differentiation, and Jak-STAT signaling pathway. The molecular docking results showed effective ingredients (quercetin, kaempferol, and 7-methoxy-2-methyl isoflavone) have good docking results with targets (IL-6, PTGS2, and TNF). The results of animal experiments showed that SGD can effectively upregulate the expression of PI3K and AKT proteins. Conclusion. This is the first in-depth study on the mechanism of SGD's treatment effect in AA using network pharmacology, and preliminary animal experiments verified that it is closely related to the PI3K/AKT signaling pathway. This finding may provide a new basis for SGD's clinical application in AA.