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Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases. Several studies have been carried out on the treatment of symptoms associated with GERD. The present study aimed to compare the effect of Psyllium seed and oral omeprazole on GERD in patients with functional constipation. In this trial, 132 patients were divided into 2 groups. The impact of omeprazole and Psyllium seed on the treatment and recurrence of GERD was studied. Among the patients, the rate of response to treatment was 89.2% (n = 58) in the Psyllium seed group, while in omeprazole group, it was 94% (n = 63; P = .31). The recurrence rates of Psyllium seed and omeprazole groups were 24.1% (n =14) and 69.8% (n = 44), respectively ( P < .001). The results showed that treatment of functional constipation by Psyllium seed in patients with GERD leads to improvement of GERD and its recurrences in comparison with omeprazole.