Background: The cardinal symptoms of gastroesophageal reflux disease include heartburn (pyrosis) and regurgitation. Conventional treatment is done by proton pump inhibitors. In Persian traditional medicine, several herbs (single or combined) have been used to treat gastrointestinal disorders. Objectives: This study aimed to assess the effects of Pistacia lentiscus (mastic) and Coriander Triphala on reflux symptoms compared to omeprazole in a double-blinded randomized clinical trial. Methods: In a double-blinded, multicenter, randomized clinical trial, we assessed the effects of Pistacia lentiscus L., Coriander Triphala, and omeprazole on the symptoms of GERD in Tabriz, Iran, in 2018 - 2019. Thus, 105 patients with GERD symptoms were assigned randomly to three groups as group A (Pistacia lentiscus L., 1000 mg/TDS), group B (Coriander Triphala, 1000 mg/TDS), and group C (omeprazole, 20 mg/day plus five placebo capsules per day). The assessments were done at the beginning and the end of the study using FSSG, VAS, RS, and GERD-HRQL questionnaires. Results: In the beginning, no significant differences were observed between the groups in the background characteristics. There was no statistically significant difference between Pistacia lentiscus, Coriander Triphala, and omeprazole in the improvement of FSSG, VAS, GERD-HRQL, and reflux scores. In all groups, the FFSG, VAS, reflux, and GERD-HRQL scores significantly decreased and improved after four weeks of intervention compared to the respective baselines. The FSSG score improvements after four weeks of intervention were 73.68%, 83.33%, and 68.62%, in groups A, B, and C, respectively. The VAS score improvements were 66.66%, 75.00%, and 62.50% in groups A, B, and C, respectively. Improvements in GERD-HRQL were 90.00%, 91.28%, and 82.00%, in groups A, B, and C, respectively. Reflux improvements were 66.66%, 80.00%, and 66.66% in groups A, B, and C, respectively. Conclusions: The results showed that Pistacia lentiscus and Coriander Triphala are as effective as omeprazole in the treatment of GERD.