Previous studies have demonstrated corilagin’s inhibitory effects on the growth of various cancer cells. Given the limited research on corilagin’s impact on ovarian cancer, a particularly deadly gynecological malignancy, this study aimed to investigate corilagin’s influence on A2780 ovarian cancer cell apoptosis and its underlying mechanisms. The goal was to evaluate corilagin’s potential as a therapeutic agent for ovarian cancer. The results of the CCK-8 assay showed that corilagin inhibited the proliferation of A2780 ovarian cancer cells while exhibiting lower toxicity to normal ovarian surface epithelial cells (IOSE-80). We found that corilagin significantly altered the A2780 cell cycle, decreasing the proportion of cells in the G0/G1 and G2/M phases and inducing cell cycle arrest in the S phase. At low concentrations, corilagin induced apoptosis in A2780 cells, accompanied by a decline in mitochondrial membrane potential and calcium influx. Transcriptome sequencing analysis identified differentially expressed apoptosis-related genes in corilagin-treated A2780 cells, primarily within the PI3K-AKT pathway. Furthermore, qPCR and Western blot results confirmed the upregulation of p53 and Bax genes and the downregulation of BCL-2. Corilagin also increased the expression of apoptotic factors caspase-9, caspase-3, PUMA, and cytochrome C, indicating its ability to induce apoptosis. Overall, corilagin effectively inhibited A2780 cell proliferation, induced cell cycle arrest, and triggered apoptosis. Its anti-tumor effect in vitro suggests its potential as a therapeutic agent for ovarian cancer A2780, especially through the PI3K/p53 pathway.