Nonalcoholic fatty liver disease (
NAFLD) is the most prevalent chronic
liver disease worldwide, ranging from
liver steatosis to
nonalcoholic steatohepatitis, which ultimately progresses to
fibrosis,
cirrhosis, and
hepatocellular carcinoma. Individuals with
NAFLD have a higher risk of developing cardiovascular and extrahepatic
cancers. Despite the great progress being made in understanding the pathogenesis and the introduction of new pharmacological targets for
NAFLD, no
drug or intervention has been accepted for its management. Recent evidence suggests that
NAFLD may be a
mitochondrial disease, as
mitochondrial dysfunction is involved in the
pathological processes that lead to
NAFLD. In this review, we describe the recent advances in our understanding of the mechanisms associated with
mitochondrial dysfunction in
NAFLD progression. Moreover, we discuss recent advances in the efficacy of mitochondria-targeted compounds (e.g.,
Mito-Q,
MitoVit-E,
MitoTEMPO, SS-31, mitochondrial uncouplers, and mitochondrial
pyruvate carrier inhibitors) for treating
NAFLD. Furthermore, we present some medications currently being tested in clinical trials for
NAFLD treatment, such as exercise, mesenchymal stem cells,
bile acids and their analogs, and
antidiabetic drugs, with a focus on their efficacy in improving mitochondrial function. Based on this evidence, further investigations into the development of mitochondria-based agents may provide new and promising alternatives for
NAFLD management.