ObjectiveTo compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia.DesignRandomised, double blind controlled trial, with central randomisation.SettingThai traditional medicine hospital, district hospital, and university hospitals in Thailand.ParticipantsParticipants with a diagnosis of functional dyspepsia.InterventionsThe interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days.Main outcome measuresFunctional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events.Results206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (−4.83, –5.46 and −6.22), non-pain (−2.22, –2.32 and −2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (−7.19, –8.07 and −8.85), non-pain (−4.09, –4.12 and −3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred.ConclusionCurcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect.Trial registration numberTCTR20221208003.