Protection of the gastric mucosa is still a relevant research question. The importance of protecting the stomach mucosa is based on the basic principles of stress theory. The two basic research approaches are the reduction of aggressive factors that act on the mucous membrane, such as an increase in pH and the eradication of Hp, and the stimulation of endogenous protective mechanisms, such as NO, PG, SH, CO and angiogenic growth factors. Peripheral and central mechanisms work in synergy for the organism to maintain the integrity of the gastric mucosa. New insights indicate that mepyramine is effective in protecting against irritating agents when administered centrally. By destroying the source of endogenous projections of brainstem dopamine neurons to the amygdala, stress lesions are exacerbated. Furthermore, protecting the gastric mucosa from ischemia-reperfusion injury and preconditioning is dependent on glucocorticoids. New therapeutic options for Hp are necessary today as increasing bacterial resistance develops. BQT is bringing more and more results as an effective therapeutic option. Hspp, often overlooked by clinicians, have shown pH dependence, where higher pH decreased their viability. PD-MSC has shown great potential in solving the problem of chronic atrophic gastritis. In the future, gastric adenocarcinomas could be treated with isocyanates alone or in combination with other chemotherapeutics. Also, ivermectin has shown the potential to treat adenocarcinoma via the WNT/B-catenin molecular pathway. NSAIDs in combination with "gaseous" mediators of cytoprotection could truly maintain the functionality of NSAIDs while reducing their complications. Pentadecapeptide BPC 157 repeatedly shows in clinical and preclinical studies its effectiveness in diseases of various etiopathogenesis, which supports the theory that the digestive system is one of the fundamental integrators of the reaction against threats to homeostasis.