The number of patients with
nonalcoholic fatty liver disease (
NAFLD)/
nonalcoholic steatohepatitis (NASH) is increasing globally and is raising serious concerns regarding the increasing medical and economic burden incurred for their treatment. The progression of NASH to more severe conditions such as
cirrhosis and
hepatocellular carcinoma requires
liver transplantation to avoid death. Therefore, therapeutic intervention is required in the NASH stage, although no therapeutic drugs are currently available for this. Several anti-NASH candidate drugs have been developed that enable treatment via the modulation of distinct signaling cascades and include a series of drugs targeting
peroxisome proliferator-activated receptor (
PPAR) subtypes (PPARα/δ/γ) that are considered to be attractive because they can regulate both systemic lipid metabolism and
inflammation. Multiple
PPAR dual/pan agonists have been developed but only a few of them have been evaluated in clinical trials for
NAFLD/NASH. Herein, we review the current clinical trial status and future prospects of
PPAR-targeted drugs for treating
NAFLD/NASH. In addition, we summarize our recent findings on the binding modes and the potencies/efficacies of several candidate
PPAR dual/pan agonists to estimate their therapeutic potentials against NASH. Considering that the development of numerous
PPAR dual/pan agonists has been abandoned because of their serious side effects, we also propose a repositioning of the already approved, safety-proven
PPAR-targeted drugs against
NAFLD/NASH.