To explore the pivotal mechanisms of Zishen Yutai Pills for the prevention and treatment of premature ovarian insufficiency(POI) based on transcriptome and bioinformatics.Methods:The POI mice models were administered with Zishen Yutai Pills(ZYP) as preventative medicine.The transcriptomes of ovarian tissue from the model and the ZYP treatment groups were sequenced by the second-generation high-throughput sequencing platform.Gene Ontology(GO) enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG) were used for biological functional enrichment analysis，and target genes were predicted by protein-protein interaction(PPI) analysis.The consistency of the predicted target gene results of the transcriptome was verified by real-time fluorescent quantitative PCR(qRT-PCR).Results:Compared with the model group，the estradiol，anti-Müllerian hormone，and ovarian coefficient increase in the ZYP treatment group，and the number of follicles in tissue in different developmental stages increases.Transcriptomics results show that there are 57 differentially expressed genes(DEGs) between the two groups.GO analysis shows that DEGs are involved in regulating complement and coagulation cascade reaction pathways，while KEGG analysis finds that DEGs are involved in cholesterol metabolism，fat digestion and absorption，and other signaling pathways.The overlapped genes，Apob，Fga，Plg，Fgb，and Apoh，between PPI and KEGG analysis results are predicted as the potential target genes.qRT-PCR results show that ZYP significantly increases the mRNA expressions of Fga and Fgb and decreases the mRNA expressions of Apob，Plg，and Apoh.Conclusion:ZYP can regulate complement and coagulation cascade reaction pathway through Fga，Plg，and Fgb and cholesterol metabolism and fat digestion and absorption through Apoh and Apob，so as to prevent and treat POI.