Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut–liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.