Cholestatic liver disease (CLD) is a range of conditions caused by the accumulation of bile acids (BAs) or disruptions in bile flow, which can harm the liver and bile ducts. To investigate its pathogenesis and treatment, it is essential to establish and assess experimental models of cholestasis, which have significant clinical value. However, owing to the complex pathogenesis of cholestasis, a single modelling method can merely reflect one or a few pathological mechanisms, and each method has its adaptability and limitations. We summarize the existing experimental models of cholestasis, including animal models, gene-knockout models, cell models, and organoid models. We also describe the main types of cholestatic disease simulated clinically. This review provides an overview of targeted therapy used for treating cholestasis based on the current research status of cholestasis models. In addition, we discuss the respective advantages and disadvantages of different models of cholestasis to help establish experimental models that resemble clinical disease conditions. In sum, this review not only outlines the current research with cholestasis models but also projects prospects for clinical treatment, thereby bridging basic research and practical therapeutic applications.