Thus, in the present study, to explore the therapeutic effect of gardenoside in NAFLD and the molecular mechanism involved, we used in vitro and in vivo NAFLD models to validate the interaction between CTCF and DPP4 and evaluated the relevant biological processes, such as lipid accumulation, intracellular ROS production, NLRP3 inflammasome, and hepatocyte pyroptosis. Here, NLRP3 is linked to metabolic dysfunction-associated steatotic liver disease.