We discuss various mechanisms of action of geniposide in the treatment of NAFLD, including decreased insulin resistance via the regulation of key molecules, such as insulin receptor substrate 1 (IRS-1) and glucose transporter type 1 (GLUT1), and the alleviation of oxidative stress via activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1  (Nrf2/HO-1) signaling pathway. Here, IRS1 is linked to metabolic dysfunction-associated steatotic liver disease.