Introduction: Functional dyspepsia (FD) is one of the most frequent gastrointestinal disorders with a high burden. Although FD is a heterogeneous disorder without any standard therapy (treatment/treatment – repetition), there is a wide history of using herbal remedies for its treatment. Two of these herbal remedies quoted in various Persian medicine resources are celery and ajwain. Their effects have been investigated in recent clinical trials in FD patients. We aimed to compare the effect of celery and ajwain to that of domperidone in patients with postprandial distress syndrome. Methods: This is a randomized double-blind active-control clinical trial, conducted at Kerman, Iran in 2020. Participants of this study were 100 patients suffering from FD (postprandial distress syndrome subtype). The intervention group received 1 g of the combination of celery and ajwain (Apium graveolens L. and Trachyspermum copticum [L.] Link), while the control group received 30 mg of domperidone per day for 4 consecutive weeks. Primary outcomes were symptom severity and frequency, and secondary outcomes were quality of life (QoL) and safety. All outcomes were assessed at the end of the trial and also 4 weeks after the trial was finished. Results: No significant differences in symptom frequency were found between groups. However, differences in symptom severity were found at the end of the follow-up (week 8) (p = 0.001). The intragroup analysis showed a significant decrease in the symptoms severity and frequency at the end of week 4 in both groups (p < 0.001). QoL in the intervention group was higher compared to the control group at the end of the study (p < 0.001) and at the point of the follow-up (week 8; p < 0.001). No serious adverse events occurred in either group. Conclusion: The herbal mixture of celery and ajwain could be considered a safe and effective remedy, decreasing the severity of symptoms and increasing QoL in patients with postprandial distress syndrome. It is further suggested to confirm these findings in high-quality multi-center clinical trials.