Ershiyiwei Lvronghao Concentrated Pills (ESYWLRHW) is the concentrated pill developed and prepared based on the classical prescription in Xizang: Ershiwuwei Lvronghao Pills (ESWWLRHW). However, its effect on nonalcoholic fatty liver disease (NAFLD) remains unclear. The aim of this study is to clarify the therapeutic effect and mechanism of ESYWLRHW on NAFLD. High-Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry/Mass Spectrometry (HPLC-Q-TOF-MS/MS) was used to analyze the components of ESYWLRHW. The NAFLD model was established by feeding Sprague-Dawley (SD) rats with high-fat diet (HFD) for ten consecutive weeks, and different doses of ESYWLRHW and positive drugs were given for intervention treatment in the last six weeks. The pathological and molecular changes of rats in each group were determined after the whole experimental procedure with pathological sections and ELISA experiments, and the metabolomics, proteomics and transcriptomics were used to investigate the possible mechanism.