BACKGROUND: Epidemiological data on the prevalence of uninvestigated dyspepsia (UD) and its impact on the health-related quality of life (HRQOL) in Indonesian population are still lacking. There is no study investigating the association between exercise and the HRQOL in UD patients. We aimed to investigate the prevalence of UD and its association with physical exercise, and its impact on HRQOL in Indonesian patients with UD. METHODS: This was a population-based, cross-sectional study, conducted using an internet-based questionnaire which was randomly distributed throughout Indonesia using the social media. The questionnaire contained socio-demographic details, exercise levels, Rome III criteria for dyspepsia, and SF-NDI (Short Form-Nepean Dyspepsia Index). The frequency, duration, the intensity of exercise, and the classification of exercise according to ACSM (American College of Sports Medicine) were included in the assessment. The screening for UD was conducted using the Rome III criteria and the SF-NDI score was calculated to assess the HRQOL in patients with UD. RESULTS: A total of 2725 valid responses were collected. The overall prevalence of UD in the study was 49.75%. Multiple logistic regression analysis showed that gender (female) and lack of exercise were independently associated with UD (OR 2.07, 95% CI 1.74-2.47, p < 0.001 and OR 1.72, 95% CI 1.42-2.07, p < 0.001). The median SF-NDI score among 1295 UD subjects in non-exercising and exercising groups was 21.00 and 18.00 (p < 0.001), respectively. CONCLUSION: This study demonstrated the prevalence of UD and the association between exercise and HRQOL among UD patients in Indonesia.