To investigate the effects of Liuwei Dihuang Pills(LWDH) on hormone levels，oxidative stress，and granulosa cell autophagy in a mouse model of premature ovarian failure(POF)，and to explore its potential mechanisms.Methods:POF in mice was induced by intraperitoneal injection of cyclophosphamide(CTX).After successful modeling，the mice were divided into the model group，low-dose LWDH group，high-dose LWDH group，estradiol valerate group，pathway inhibitor group(NVP-BEZ235)，and pathway inhibitor+high-dose LWDH group.Mice were administered by gavage for 28 days.Hormones and oxidation-related markers in serum were measured using enzyme-linked immunosorbent assay(ELISA)，including anti-Müllerian hormone(AMH)，estradiol(E2)，luteinizing hormone(LH)，follicle-stimulating hormone(FSH)，superoxide dismutase(SOD)，glutathione peroxidase(GSH-Px)，and malondialdehyde(MDA).After euthanizing the mice，the ovaries were weighed to calculate the ovarian index.Hematoxylin-eosin(HE) staining was used to assess pathological changes in ovarian tissues.Immunohistochemistry was used to detect the content of microtubule-associated protein light chain 3(LC3) in ovarian tissues，and autophagosome counts were assessed by transmission electron microscopy to evaluate autophagy.Western blot and qPCR were performed to detect the expression of autophagy-related and signaling pathway-related proteins and genes.Results:Compared to the model group，the high-dose LWDH group showed significant increases in E2，AMH，SOD，and GSH-Px(P<0.05)，and significant decreases in FSH，LH，and MDA(P<0.05).The ovarian index was significantly increased(P<0.05)，the number of corpora lutea was increased，and the number of atretic follicles was reduced(P<0.05).Autophagosome counts were significantly decreased，and the autophagy marker LC3 was reduced，while sequestosome 1(P62)，phosphorylated phosphatidylinositol 3-kinase/total phosphatidylinositol 3-kinase(p-PI3K/PI3K)，and phosphorylated protein kinase B/total protein kinase B(p-AKT/AKT) were significantly increased(P<0.05).Conclusion:LWDH protect the ovaries from CTX-induced ovarian damage and oxidative stress.The possible mechanism of action involves the activation of the PI3K/AKT/mTOR pathway，which inhibits excessive autophagy in granulosa cells and improves ovarian function.