Objective To analyze the multisystem damage and genetic characteristics of Alagille syndrome. Methods Data of 8 cases diagnosed with Alagille syndrome collected from December 2018 to May 2025 were retrospectively analyzed. Their clinical features, diagnostic and treatment processes, and outcomes were summarized. Results Among the 8 patients, 3 were males and 5 were females. Cases 1 to 5 were probands of their families. They were diagnosed aged 4 months to 17 years old. All 5 probands presented with jaundice of the skin and sclera, and liver damage, which was consistent with cholestasis. Three probands had cardiac defects such as atrial septal defect, pulmonary stenosis, and ventricular septal defect, and renal abnormalities such as IgA nephropathy, renal cysts and renal hypoplasia, distinctive facial features and developmental delays (short stature). Three probands had butterfly vertebrae and splenomegaly. One case had diabetes. All 8 patients were detected with JAG1 gene variations, including 3 missense, 1 nonsense and 1 microdeletion. Among them, 4 variations were novel. The condition of 5 probands stabilized after dietary and metabolic treatment. Cases 6, 7, and 8 were mothers of 3 probands, respectively. They carried the same variations as in the probands and developed diabetic retinopathy, diabetic nephropathy, pulmonary stenosis, and hypertriglyceridemia, respectively. Conclusions The patients of Alagille syndrome present with multisystem damage. Cholestatic liver disease is the primary manifestation. IgA nephropathy and diabetes are rare phenotypes. Genetic testing is the key for diagnosis.