This study aims to observe the improvement of non-alcoholic steatohepatitis(NASH) after using water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata and explore their preliminary mechanism. Mice were fed with methionine-choline-deficent diet(MCD) for 6 weeks for modeling, and mice were orally given with 50, 100, 200 mg·kg~(-1) of Polygoni Multiflori Radix water extract(PMRWE) or Polygoni Multiflori Radix Praeparata water extract(PMRPWE) at the last 4 weeks. During the whole experimental procedure, the body weight changes of the mice were monitored and recorded. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activities were detected; liver histopathological evaluation and NAFLD activity score(NAS) calculation were conducted, and the levels of reactive oxygen species(ROS) in liver tissues were analyzed. The contents of triglyceride(TG) and non-esterified fatty acids(NEFA) in liver tissues were detected, and oil red O staining of the liver tissues was conducted and observed. Quantitative polymerase chain reaction(qPCR) was used to detect hepatic mRNA expression of β-oxidation-related genes in mice. The results showed that PMRWE(100, 200 mg·kg~(-1)) and PMRPWE(50, 100, 200 mg·kg~(-1)) alleviated liver damage in MCD-induced NASH in mice. PMRWE(100, 200 mg·kg~(-1)) and PMRPWE(50, 100, 200 mg·kg~(-1)) reduced hepatic li-pid accumulation in mice with NASH. Different doses of PMRPWE inversed the decreased hepatic mRNA expression of β-oxidation-related genes in mice with NASH. This study indicated that PMRPWE and PMRWE could ameliorate MCD-induced NASH in mice by promoting fatty acid β oxidation, reducing liver lipid accumulation, and alleviating liver damage. Moreover, the protective effect of PMRPWE against MCD-induced NASH was better than PMRWE.