Side effects and chemotherapy resistance, demand new therapeutics with minimal side effects. Here, we investigated the combined effect of curcumin and metformin on the LNCaP prostate cancer cell line. LNCaP cells were treated with curcumin, metformin, and their combination at different concentrations. Cell viability was assessed by MTT assay and expression ofBax, Bcl-2, mTOR, hTERT, PUMA, p53andp21genes was analyzed by real-time PCR. Apoptosis and cell cycle were assessed by flow cytometry. Our results revealed that the viability of cells treated with curcumin, metformin, and their combination was significantly (P < 0.05) reduced with increasing the concentration and prolonging the treatment time. Meanwhile, the combination showed a synergistic effect within 48 h. In the curcumin treated group, the expression ofBcl-2andhTERTgenes diminished. In the metformin treated group, the expression ofBaxandPUMAgenes was enhanced while the expression ofBcl-2,hTERT,mTOR, andp53genes declined. Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression ofBaxgene. The combination of curcumin and metformin showed synergistic effects within 48 h. This combination could be a potential therapeutic candidate for prostate cancer to be further investigated.