Background: Leptomeningeal metastasis of gastric adenocarcinoma (LM-GC) is a rare and severe complication with a poor prognosis, its prognosis is significantly poorer than liver, lung, and peritoneal metastases. Studies on LM-GC have been limited to clinical case reports. Despite advances in systemic therapies, there is a lack of standardized treatment protocols for LM-GC due to its rarity and the challenges it presents.Methods: This case series reports on six patients diagnosed with LM-GC who received intrathecal methotrexate (MTX) injection from June 2018 to November 2023. Treatment efficacy, safety, and prognostic factors were analyzed by comparing symptoms and laboratory test results before and after treatment.The average OS for the cohort was 7.5 months, exceeding previous reports for LM-GC patients, which has a median survival time of 4-6 weeks. No significant changes were observed in cerebrospinal fluid glucose and chloride levels post-MTX treatment. However, a statistically significant decrease in cerebrospinal fluid protein levels was noted after treatment (P < 0.05). Adverse reactions were mild, with the most common being bone marrow suppression and oral mucosal ulcers.Intrathecal MTX injection combined treatment offers a potential therapeutic strategy for LM-GC, improving clinical symptoms and extending survival. Further research is warranted to validate these findings and explore the molecular mechanisms of LM-GC for targeted therapies.