Gastric cancer (GC) is one of the most common cancers and the second leading cause of cancer-related mortality. Increasing discoveries have highlighted aberrant epigetic modifications actively contribute to the pathogenesis of this fatal disease. Among these epigenetic events, dysregulated methylation is particularly associated with GC progression. Importantly, these aberrant methylation modifications caused by the misregulation of methyltranferases are frequently reversible, which provides opportunities for targeted treatment using specific molecular inhibitors. In the present review, we provide an overview of the current literature on the changes of DNA and histone methylations that alter gene expressions in GC and describe the emerging targeted epigenetic therapy in GC.