Despite the efficacy of fluoropyrimidines and oxaliplatin-based chemotherapy for patients, this treatment leads to significant patient inconvenience, toxicity, and cost. This study aims to validate a nontoxic agent, curcumin, to the current chemotherapeutic regimen. In in vitro experiments, curcumin induced apoptosis in gastric cancer cell line BGC-823. Synergistic antitumor effects of curcumin were observed in combination with 5-fluorouracil (5-FU) and oxaliplatin. These effects were accompanied by downregulation of the expression of Bcl-2 protein and mRNA and upregulation of the expression of Bax and caspase 3, 8, and 9. In addition, the in vivo study showed that the combination of curcumin and 5-FU/oxaliplatin exhibited potent growth inhibition of BGC-823 xenograft tumors. Furthermore, compared with the control group, no significant difference was observed in the body weight of curcumin-treated nude mice. In conclusion, curcumin may act synergistically with the chemotherapeutic regimen FOLFOX in gastric cancer in vitro and in vivo by inducing apoptosis via Bcl/Bax-caspase 8,9-caspase 3 pathway.