Many outpatients with functional dyspepsia (FD) do not follow the medication schedule recommendations, which can lead to illness relapse. To investigate whether short message service (SMS) reminders improve medication regimen adherence and therapeutic efficacy in outpatients with FD. Participants with FD were randomly allocated to the control group or intervention group. Patients in the control group received a 4-week medication treatment with no reminders, those in the intervention group received medication treatment plus a daily SMS reminder of dose and medication time. Newly diagnosed FD patients from April 2019 to June 2019 were recruited from the GI outpatient clinics at Renji Hospital. The scores for FD symptoms (LDQ) and psychological conditions (PHQ-9 for depression and GAD-7 for anxiety) were assessed before and after the treatment. The medication possession ratio (MPR) was calculated. A total of 352 eligible patients was enrolled in the study. The overall compliance rates of patients in the intervention and control groups were 87.5% and 80.7% in the intention-to-treat (ITT) analysis (P = 0.08) and 94.48% and 86.59% in per-protocol (PP) analysis (P = 0.015), respectively. In the intervention group, the compliance rate of younger patients (age ≤ 40years) was significantly higher than that of age-matched patients in the control group (ITT: 86.1% vs. 70.5%, P = 0.018). Compared with the control group, the reduction in scores of LDQ (9.33 vs. 8.02, P = 0.017), PHQ-9 (6.97 vs. 5.69, P = 0.004), and GAD-7 (8.70 vs.7.53, P = 0.028) was significantly greater in patients receiving SMS reminders. The MPR of patients positively correlated with the reduction in scores of LDQ, PHQ-9, and GAD-7 in both groups. SMS reminders can improve treatment compliance and efficacy in patients with FD. NCT04052750.