Proton pump inhibitors (PPIs) are widely used in digestive system diseases, but long-term use of PPI may cause Clostridium difficile infection, small intestinal bacterial overgrowth, spontaneous bacterial peritonitis and gastrointestinal barrier dysfunction. Probiotics can improve the digestive tract microecological disorder caused by the application of PPI by inhibiting the colonization of bacteria in the intestinal tract, regulating the body’s immunity, reducing the pH value of the intestinal tract, and enhancing the barrier function of the intestinal mucosa. This article elaborates on the influence of PPI on the microecology of the digestive tract and the regulation of probiotics on the microecology of the digestive tract, aiming to provide some ideas for the digestive tract microecological disorders caused by the application of PPI in clinical practice and their intervention strategies.