Digestive diseases encompass a spectrum of disorders affecting the digestive organs, ranging from benign to severe conditions. The diagnosis and treatment of various chronic digestive diseases pose inherent challenges, underscoring the urgent need for noninvasive early biomarkers. Without homeostasis mechanisms, urine is an ideal source of biomarkers, theoretically capable of reflecting early changes of disease. In this section, we will introduce the new studies of the urine proteome in rat models of three digestive diseases include liver fibrosis, chronic pancreatitis, and inflammatory bowel disease. These investigations have uncovered numerous potential biomarkers that manifest prior to the onset of clinical symptoms and significant pathological changes, providing important clues for the early detection of these diseases. We think the urine proteome has a broad application prospect in the early diagnosis, treatment, monitoring, and prognosis of digestive diseases.