<i>Background:</i> Based on several phase III studies, oral S-1-based chemotherapy has become the standard for treatment of advanced gastric cancer in Japan. However, these studies included patients able to maintain sufficient oral intake, and the effectiveness of chemotherapy for patients unable to eat remained unclear. <i>Methods:</i> We retrospectively analyzed the effect of chemotherapy on patients with advanced gastric cancer who presented with inability to eat. We defined ‘inability to eat’ as requirement for daily intravenous fluids or hyperalimentation and ‘improvement of oral intake’ as no such requirement >1 week. <i>Results:</i> Among the 777 patients who received first-line chemotherapy, 100 patients (12.8%) were considered unable to eat and required daily intravenous fluids or hyperalimentation. Performance status was 0–1 in 26 patients and ≧2 in the other 74 patients. Seventy-eight patients (78%) had peritoneal metastasis and 62 patients (62%) had ascites. First-line chemotherapy with 5-fluorouracil-based regimens was used in 46 patients, taxane-based chemotherapy in 34 patients, oral fluoropyrimidine-based therapy in 19 patients, and irinotecan-cisplatin combination treatment in 2 patients. Median survival time was 5.0 months (95% confidence interval, CI, 3.9–6.6). Improvement in oral intake with duration for >1 week was achieved in 40 patients (40%) with the median duration of nutritional-support-free time of 3.1 months (95% CI 2.5–4.6). <i>Conclusion:</i> Chemotherapy is moderately effective in improving oral intake in patients with advanced gastric cancer with inability to eat. Further study is required to improve its prognosis.