Objective To investigate the effects of fenofibrate and simvastatin on liver lipid accumulation and mitochondrial function-related signaling pathways in non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet. Methods Forty male 6-week-old C57BL/6J mice were randomly and equally assigned into four groups: Control group (normal diet), High fat diet group (14 weeks of a high fat diet), Fenofibrate group (14 weeks of a high fat diet and administered 0. 04 g/ (kg·d) fenofibrate by gavage at 11 weeks for 4 weeks), and Simvastatin group (14 weeks of a high fat diet and administered 0. 004 g/ (kg·d) simvastatin by gavage at 11 weeks for 4 weeks). This study verified the role of mitochondrial functions in the pathogenesis of NAFLD by changes in body weight, liver weight, liver index, serum biochemical indexes, pathological changes of the liver, oxidative stress indicators, mitochondrial function indexes, and related signaling pathways. It also explored the effects of fenofibrate and simvastatin on mitochondrial functions in NAFLD model mice. Results There were significant differences between NAFLD model and control groups in terms of body weight, liver weight, liver index, serum biochemical indexes, oxidative stress indicators, pathological changes of the liver, and mitochondrial function indexes ( P< 0. 05). Fenofibrate and simvastatin improved these objective indicators. Conclusions Fenofibrate and simvastatin upregulated the PPARα/ PGC-1α signaling pathway related to mitochondrial functions, promoted mitochondrial β oxidation, and reduced oxidative stress damage and lipid accumulation in the liver.