L-ornithine L-aspartate (LOLA) has been known as an effective ammonia-lowering agent for more than 50 years with good evidence in hepatic encephalopathy. Administration of LOLA removes ammonia via two distinct mechanisms: by synthesis of urea and by the synthesis of glutamine via the enzyme glutamine synthetase. While LOLA has been used in cirrhosis and acute liver injury settings, it is less clear if LOLA could be used in non-alcoholic fatty liver disease (NAFLD). NAFLD and the progressive form non-alcoholic steatohepatitis (NASH) are currently the leading causes of chronic liver disease worldwide, with roughly 25% of the world population affected by NAFLD. Consequences of NASH are end-stage liver disease and cardiovascular morbidity and mortality. As the basis for NAFLD is excess calorie uptake and excess adipose tissue mass, the conservative therapeutic approach is weight loss by intense lifestyle change. However, no pharmacological treatment options are currently approved. LOLA is being investigated as a pharmacological tool to ameliorate liver injury in NAFLD on the basis that it lowers liver ammonia concentrations and supplies anti-oxidative glutamine and glutathione. Indirect hepatoprotective effects currently under investigation could also be beneficial.