Advanced maternal age and ovarian aging are deleterious to the quantity and quality of oocytes and epigenetic modifications, which can affect the health of offspring. However, relatively little is known about the regulation of microRNA‐mediated transcription during ovarian aging. We therefore aimed to identify age‐related mRNA and microRNA changes and their interactions in the ovaries of aged mice. We performed QuantSeq 3′mRNA and small RNA sequencing to compare their expression patterns in post‐ovulation ovaries from young (12‐week‐old) and old (44‐week‐old) mice. Functional annotation and integrative analyses were performed to identify the potential functions of differentially expressed genes and identify binding sites for critical microRNAs. We found 343 differentially expressed genes and 9 microRNAs in our comparison of the two mouse groups, with fold changes >2.0 (
P
< 0.01). Furthermore, we identified possible direct interactions between 24 differentially expressed mRNAs and 8 microRNAs. The differentially expressed genes are involved in fat digestion and absorption, the PI3K‐Akt signaling pathway, serotonergic synapse, and ovarian steroidogenesis, which are important for folliculogenesis and oocyte growth. During ovarian aging, changes in gene expression induce alterations in folliculogenesis, oocyte growth, and steroidogenesis, resulting in decreased oocyte quality and reproductive outcomes.