Gastroesophageal reflux disease (GERD) is one of the most widespread gastrointestinal pathologies and the most common reason for seeking medical care at the level of a primary link of public health services in many countries around the world. The classic clinical presentations of GERD are heartburn, belching, and regurgitation (spitting up), but the overall spectrum of GERD symptoms is broader and more heterogeneous in scope, including extraesophageal symptoms. Clinical and/or endoscopic refractoriness of some patients to the standard proton pump inhibitors (PPIs) therapy remains a global challenge in the management of patients with GERD at the current stage of clinical medicine development. A medicinal product of a fundamentally new class was developed to optimize the treatment of patients with GERD – an esophageal mucosal protectant, which consists of a fixed combination of hyaluronic acid and chondroitin sulfate dissolved in a bioadhesive carrier (polymerase 407). This review is primarily aimed at systematizing data on the efficacy of the esophageal mucosal protectant in the treatment of patients with GERD. The systematic review that summarized the results of 10 studies involving 1090 patients with GERD showed that adding this esophageal mucosal protectant to the PPI therapy increased the efficacy of GERD therapy, as well as improved the frequency of symptomatic, endoscopic and morphological response to the treatment. Such combination therapy contributes to the optimization of the treatment of patients with various disease phenotypes, regress of both esophageal and extraesophageal symptoms, and potentiation of repair of the esophageal mucosa. To increase the efficacy of treatment and improve the prognosis of the disease, this approach should be implemented at the early stages of therapy in real clinical practice.