One of the most common chronic conditions of peptic ulcer is gastric ulcer (GU), which is recognized as a high-risk illness in the present-day lifestyle. Originating from Asia and Europe, Beetroot (Beta vulgaris L.) is packed with high amounts of bioactive compounds like betanin and phenolics. These contribute to its nutritional value and overall health benefits. In this work, varying concentrations (0.5% to 7% w/v) of beta-cyclodextrin (β-CD) and hydroxypropyl-beta-cyclodextrin (HP-β-CD) were used to improve the efficiency of extracting beetroot components with water, using both stirring and ultrasound techniques. The presence of 5% (w/v) HP-β-CD during extraction appeared the maximum values of total phenolic compounds and betanin (3.1 mcg/mL and 3.01 mg/mL, respectively). The extraction recoveries of betanin at 5% (w/v) HP-β-CD emerging with magnetic stirring were 73%, 36% and 50% against water, ethanol and β-CD, respectively. The reproducibility of extraction procedure was found to be 0.86% relative standard deviation (RSD) indicating the highest precision of the beetroot modified HP-β-CD extraction procedure. Then, rats that had been treated with either HP-β-CD-modified aqueous extract of beetroot, omeprazole (20 mg/kg, orally administered) or both were studied to assess whether they helped reduce ethanol-induced GU. The combined treatment of HP-β-CD modified beetroot extract with omeprazole brought a significant decrease in the increased levels of serum oxidative stress malonaldehyde and nitric oxide, inflammatory markers myeloperoxidase, interleukin-10, interleukin-6 and tumor necrosis factor-α. It also restored the decreased levels of antioxidant glutathione and cyclo-protective prostaglandin E2 in comparison to the positive control. Furthermore, the proposed combination of beetroot-modified aqueous extract and omeprazole exhibited less severe histopathological damage in comparison to the positive control. Therefore, a novel synergistic pharmaceutical treatment using HP-β-CD modified aqueous extract of beetroot and omeprazole was presented to enhance GU healing.