Natural ovarian aging is one of the major causes for declining fertility in female animals, which has become an insurmountable issue in human reproduction clinics and assisted reproductive technology procedures. Nevertheless, the molecular basis of oocyte aging remains poorly understood, and feasible improvement strategies are unavailable. In the present study, in vivo supplementation of pyrroloquinoline-quinone effectively elevated the fecundity of reproductively aged mice by balancing hormonal secretion, harmonizing the estrus cycle, and eliminating ovarian fibrosis. Moreover, oocyte quality also increased in aged mice after pyrroloquinoline-quinone administration from various aspects, including nuclear and cytoplasmic maturation competency, fertilization capacity, and pre-implantation embryonic development potential. Transcriptomic analysis identified target pathways that might mediate pyrroloquinoline-quinone's effects in aged oocytes. Specifically, it was demonstrated that pyrroloquinoline-quinone supplementation restored the mitochondrial dynamics and lysosomal function to remove excessive reactive oxygen species and suppress apoptosis in aged oocytes. Jointly, these findings demonstrate pyrroloquinoline-quinone administration is an efficacious method to restore the compromised ovary function and damaged oocyte quality in reproductively aged mice, which might be a potential clinical therapy for women of advanced maternal age with infertility.