Background: Gastroesophageal reflux disease (GERD) is a common disorder that may result in esophageal cancer. Although proton pump inhibitors are the standard treatment for this illness, Brassica oleracea may provide new therapeutic possibilities. Objectives: We aimed to evaluate and compare the effects of the B. oleracea extract and the proton pump inhibitor omeprazole on esophageal complications arising from a surgically-induced GERD model in rats. In addition, we investigated possible associations between the frequency of DNA damage and esophageal histological alterations, as well as the genotoxic/anti-genotoxic and cytotoxic/anti-cytotoxic effects of B. oleracea and omeprazole. Methods: Rats with and without GERD were equally divided into groups to receive one of two the treatments, B. oleracea extract (500 mg/kg bw) or omeprazole (30 mg/kg bw), daily over the course of four weeks. A group of non-treated rats received water in the same circumstances. Micronucleus assay was used to assess DNA damage in blood and bone marrow cells. Results: Rats with GERD developed esophagitis and esophageal squamous cell carcinoma. B. oleracea and omeprazole-treated GERD rats presented significantly decreased inflammation in relation to non-treated GERD rats (P < 0.05). However, in rats without GERD, omeprazole significantly increased the frequencies of micronuclei and micronucleated cells as compared to the corresponding cell counts in non-treated rats (P = 0.04). Conclusions: B. oleracea demonstrated similar anti-inflammatory properties to omeprazole in rats with GERD. However, omeprazole also demonstrated genotoxic and cytotoxic effects in rats without GERD.