Saponins are plant-derived amphiphilic glycosides known for their diverse pharmacological activities, including anticancer effects. Afrocyclamin A, an oleanane-type triterpene saponin isolated from A. umbellata, has been shown to induce cancer cell death by suppressing the PI3K/AKT/mTOR signaling pathway. Moreover, several studies have reported that docetaxel exhibits enhanced anticancer efficacy when administered in combination with PI3K/AKT/mTOR pathway inhibitors. In this study, we evaluated the anticancer effects of combining afrocyclamin A with docetaxel in human prostate cancer cell lines, including LNCaP, DU145, and PC-3. The most pronounced anticancer effect was observed in PC-3 cells after 48 h of treatment. Furthermore, co-treatment with afrocyclamin A and docetaxel for 48 h significantly increased the proportion of apoptotic cells and induced G2/M phase cell cycle arrest, as assessed by flow cytometry. The combination treatment also suppressed phosphorylation of the PI3K/AKT/mTOR signaling pathway. In addition, cell migration and colony formation were inhibited in PC-3 cells after combined treatment. Taken together, these findings indicate that the combination of afrocyclamin A and docetaxel exerts anticancer activity in PC-3 cells, at least in part through inhibition of the PI3K/Akt/mTOR signaling pathway.