Objective To investigate whether adoptive transfer of regulatory T cells (Treg cells) overexpressing Pellino-1 (Peli1) can repair the ovarian function of mice with autoimmune premature ovarian insufficiency (POI) and regulate its immune function. Methods The autoimmune POI mouse model was constructed using zona pellucida 3 peptide (pZP3), and the lentiviral vector overexpressing Peli1 (LV-Peli1) was constructed. Then LV-Peli1 was transfected into Treg cells, and finally the Treg cells overexpressing Peli1 were adoptively transferred into the model mice. The POI model mice were randomly divided into 4 groups (5 in each group), namely, LV-Peli1-POI group (Treg cells overexpressing Peli1 were adoptively transferred to POI mice), LV-POI group (Treg cells transfected with empty-vector lentivirus were adoptively transferred to POI mice), Treg-POI group (Treg cells without any treatment were adoptively transferred to POI mice) and POI model group (an equal volume of phosphate-buffered saline was injected into POI mice via the tail vein). Hematoxylin-eosin staining was used to observe the ovarian structures and follicle counts at various stages of mice in each group. Immunohistochemical staining was used to detect the levels of proliferation protein Ki-67 and CD3^＋ T lymphocytes in ovarian tissue, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to detect the apoptosis of granulosa cells in ovarian. Enzyme-linked immunosorbent assay was used to detect the expression levels of serum ovarian hormones follicle-stimulating hormone (FSH), estradial (E₂), and cellular immune factors interleukin 10 (IL-10) and transforming growth factor β (TGF-β) in mice in each group, so as to explore the effect of Peli1 overexpression on autoimmune POI. Results Compared with the LV-POI group, Treg-POI group and POI model group, the numbers of primordial follicles, primary follicles, secondary follicles and mature follicles were significantly increased, the expression of Ki-67 was significantly increased, the apoptosis of ovarian granulosa cells was significantly reduced, the expression level of FSH was decreased, and the expression level of E₂ was significanly increased in the LV-Peli1-POI group (P＜0.05, P＜0.01). The level of CD3^＋ T lymphocytes in the LV-Peli1-POI group was significantly decreased, and the expression levels of IL-10 and TGF-β were significantly increased (P＜0.05, P＜0.01). Conclusion Adoptive transfer of Treg cells overexpressing Peli1 can effectively promote the proliferation of POI ovarian granulosa cells of mice and inhibit their apoptosis. At the same time, it can improve the ovarian endocrine function and regulate immune function in POI mice, thereby producing a certain repairing effect on autoimmune POI.