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Equine squamous gastric disease (ESGD) most notably affects Thoroughbred racehorses, with a prevalence of 80–100 %. Omepra zole, the treatment of choice, has been extensively investigated in the past. However, the drug's withdrawal time is 9 days for racehorses in Germa ny, prohibiting its use before racing. Despite an emerging interest in vital mushrooms to treat gastric ulcers in humans, no studies have yet been published in horses. The aim of the current study was to compare an orally administered vital mushroom formulation with an orally administered buffered omeprazole powder paste formulation with regard to their impact on equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD). After clinical and gastroscopic examination, 22 Thoroughbred young racehorses (mean ± SD age 25.7 ± 1.46 months) with lesions of the squamous and/or glandular mucosa were assigned to one of two groups. Horses received either vital mushrooms orally (CME Gastric Control Gold, CME Horses GmbH, Münster, Germany; n = 10 horses) at a dosage of 30 grams/horse for 28 days or buffered paste omeprazole orally (GastroGard®, Boehringer Ingelheim, Ingelheim am Rhein, Germany; n = 12 horses) at an initial dosage of 4 mg/kg bwt for 7 days and a cost limiting prophylactic dose of 1 mg/kg bwt for the subsequent 21 days per os once daily. After completion of the 28-day treatment duration, gastric examinations were repeated to determine lesion status. While ESGD was detected in 21 out of 22 horses, EGGD was less com monly diagnosed in a total of 16 out of 22 horses. Median squamous lesion scores (plus 25th–75th percentiles) significantly improved in horses receiving omeprazole. At the beginning of the study the squamous greater curvature revealed a median score of 2 (1–3) and a median score of 1 (0–3) after treatment on day 28 (p = 0.016). The squamous lesser curvature revealed a median score of 3 (2–3) at the beginning of the study and a median score of 2 (1–3) after treatment on day 28 (p = 0.011). No statistical significance was detected in the vital mushrooms group with a squamous greater curvature median score of 1 (0–1) at the beginning of the study and a median score of 1 (0–1) after 28 days. The squamous lesser curvature in this group revealed a median lesion score of 1 (1–2) at the beginning of the study and a median lesion score of 1 (0–2) after 28 days of treatment. No statistically significant effects of either of the two treatments were observed in the fundus, antrum, and pylorus. This pilot study shows that the treatment of ESGD with vital mushrooms was inferior to treatment with omeprazole. However, gastroscopic findings did not deteriorate under treatment with vital mushrooms, which might propose their use as supplement before racing. However, due to the missing implementation of a negative control group, we cannot draw a conclusion about whether vital mushrooms supplementation reveals a difference when compared to no treatment. The small number of animals per group constitutes the main limitation of this study. For future trials, the severity of lesions should be balanced between both treatment groups as part of a randomized controlled study.