INTRODUCTION: Liquorice (Glycyrrhiza glabra) is a traditional herbal remedy with various pharmacological activities mainly used for digestive and respiratory ailments. GutGard® is a flavonoid-rich, deglycyrrhizinated liquorice root extract and is standardized to glabridin (≥3.5% w/w), and others viz., glabrol, eicosanyl caffeate, docosyl caffeate, and total flavonoids (≥10% w/w) with glycyrrhizin (≤3.0% w/w) as glycyrrhizin causes electrolyte imbalance, hypertension, and water retention. Hence, the objective of the current study was to assess the efficacy, safety, and tolerability of GutGard® in managing gastroesophageal reflux (GER)-related symptoms when compared to placebo. METHODS: It was a double-blind, parallel group, randomized, placebo-controlled trial with participants randomized in a 1:1 ratio to either the placebo group or GutGard® group. The duration of the interventions/treatment was for 28 days and the follow-up visits were done at day 7, day 14, day 28, and day 35. A telephonic follow-up was also done on day 21. The primary outcome measures studied was the change in the Gastroesophageal Reflux Disease-Health-Related Quality of Life and the Gastroesophageal Reflux Disease Symptom Assessment Scale. RESULTS: We screened a total of n = 296 participants and enrolled n = 200 participants and obtained written, informed consent from them. Participants in the GutGard® group reported a significantly better quality of life at the end of the intervention period (p = 0.014). They also reported earlier resolution of symptoms of GER as against the placebo group, especially the symptoms of heartburn (p = 0.017 on day 14 and p = 0.005 on day 28) and regurgitation (p = 0.025 on day 7, p = 0.029 on day 14, and p = 0.022 on day 28). CONCLUSIONS: The GutGard® group showed better and earlier resolution (within 2 weeks) of symptoms of GER as against the placebo group, especially heartburn and regurgitation. INTRODUCTION: Liquorice (Glycyrrhiza glabra) is a traditional herbal remedy with various pharmacological activities mainly used for digestive and respiratory ailments. GutGard® is a flavonoid-rich, deglycyrrhizinated liquorice root extract and is standardized to glabridin (≥3.5% w/w), and others viz., glabrol, eicosanyl caffeate, docosyl caffeate, and total flavonoids (≥10% w/w) with glycyrrhizin (≤3.0% w/w) as glycyrrhizin causes electrolyte imbalance, hypertension, and water retention. Hence, the objective of the current study was to assess the efficacy, safety, and tolerability of GutGard® in managing gastroesophageal reflux (GER)-related symptoms when compared to placebo. METHODS: It was a double-blind, parallel group, randomized, placebo-controlled trial with participants randomized in a 1:1 ratio to either the placebo group or GutGard® group. The duration of the interventions/treatment was for 28 days and the follow-up visits were done at day 7, day 14, day 28, and day 35. A telephonic follow-up was also done on day 21. The primary outcome measures studied was the change in the Gastroesophageal Reflux Disease-Health-Related Quality of Life and the Gastroesophageal Reflux Disease Symptom Assessment Scale. RESULTS: We screened a total of n = 296 participants and enrolled n = 200 participants and obtained written, informed consent from them. Participants in the GutGard® group reported a significantly better quality of life at the end of the intervention period (p = 0.014). They also reported earlier resolution of symptoms of GER as against the placebo group, especially the symptoms of heartburn (p = 0.017 on day 14 and p = 0.005 on day 28) and regurgitation (p = 0.025 on day 7, p = 0.029 on day 14, and p = 0.022 on day 28). CONCLUSIONS: The GutGard® group showed better and earlier resolution (within 2 weeks) of symptoms of GER as against the placebo group, especially heartburn and regurgitation.