Background and Aim The aim of this study is to identify gastric cancer burden in Indigenous Taiwanese peoples and conduct a project to evaluate how to reduce the disparities most effectively in Indigenous communities. Methods First, we quantified the health disparities in gastric cancer in Indigenous peoples using data from the cancer registries during the period of 2006–2014. Second, we identified parameters that might be associated with Helicobacter pylori infection or help identify a good eradication strategy. Results Gastric cancer incidence (24.4 vs 12.3 per 100 000 person‐years) and mortality rates (15.8 vs 6.8 per 100 000 person‐years) were higher in Indigenous than in non‐Indigenous, with 2.19‐fold (95% confidence interval CI: 2.06–2.33) and 2.47‐fold (2.28–2.67) increased risk, respectively. In Indigenous communities, H. pylori infection was more prevalent in Indigenous than in non‐Indigenous (59.4% vs 31.5%, P < 0.01). Regression analyses consistently showed that either the mountain or plain Indigenous had 1.89‐fold (95% CI: 1.34–2.66) and 1.73‐fold (95% CI: 1.24–2.41) increased risk for H. pylori infection, respectively, as compared with non‐Indigenous, adjusting for other baseline characteristics. The high infection rates were similarly seen in young, middle‐aged, and older adults. Program eradication rates using clarithromycin‐based triple therapy were suboptimal (73.7%, 95% CI: 70.0–77.4%); the habits of smoking (1.70‐fold, 95% CI: 1.01–2.39) and betel nut chewing (1.54‐fold, 95% CI: 0.93–2.16) were associated with the higher risk of treatment failure. Conclusion Gastric cancer burden is higher in Indigenous Taiwanese peoples than in their non‐Indigenous counterparts. Eliminating the prevalent risk factor of H. pylori infection is a top priority to reduce this health disparity.