Background: This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic gastric cancer (MGC) as a salvage chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with gastric cancer were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In pemetrexed based regimens, 4 clinical studies including 171 patients with advanced gastric cancer were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 25.1% (43/171) in pemetrexed based regimens. Major adverse effects were neutropenia, anorexia, fatigue, and anemia. No treatment related death occurred in pemetrexed based treatment. Conclusion: This systemic analysis suggests that pemetrexed based regimens are associated with mild activity with good tolerability in treating patients with MGC.