Abstract: Mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) gastric cancer represents a distinct molecular subtype of tumors characterized by pronounced sensitivity to immune checkpoint inhibitors (ICIs) attributed to its unique immune microenvironment and elevated mutation burden. Various clinical studies underscore the efficacy of ICIs in treating dMMR/MSI-H gastric cancer; however, challenges such as primary and acquired resistance persist. Overcoming resistance and identifying optimal ICIs for its treatment remain critical clinical issues. This review delineates the mechanisms of ICIs, recent advances in their therapeutic application for dMMR/MSI-H gastric cancer, and ongoing challenges in combating resistance, aiming to guide clinical practice effectively.