Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease that presents with steatosis, inflammation, and fibrosis and can progress to cirrhosis and cancer. Thus, methods for controlling this lifestyle-related disease are urgently needed. An extract of Siraitia grosvenorii (Luo-Han-Guo) (luohanguo extract (LE)) is widely used as a sweetener; its major bioactive constituents, mogrosides, have shown anti-oxidative and anti-inflammatory properties, exerting multiple pharmacological effects in various disorders. In the present study, we investigated the effects of LE on NASH induced in mice fed a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet without trans fatty acids (CDAA-HF- T(−)). Mice were fed with CDAA-HF- T(−) and drinking water containing LE at concentrations of 0%, 0.2%, 0.6%, and 2% for 28 weeks. Our results showed that LE was not toxic under the experimental conditions evaluated. In the liver of mice fed CDAA-HF- T(−), LE did not affect steatosis or early phase events from macrophage recruitment to hepatocyte death but inhibited late phase events, the progression of inflammation, and fibrosis (mechanisms independent of transforming growth factor-β signaling). Sweeteners with beneficial biological functions, such as LE, may be useful for controlling lifestyle-related diseases, such as NASH, and promoting human health.