In neonates, bilirubin tends to be deposited in body tissues, especially the skin and mucous membranes. Jaundice is an early symptom of bilirubin excretion disorders. Therefore, the aim of this study was to investigate the effect of clofibrate on reducing neonatal jaundice. In this systematic review, international databases, including PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar, were searched without time and language restrictions. The reference lists of all studies ultimately included were manually searched. In the 17 articles reviewed, with a sample size of 665 people published between 2005 and 2019, the average weight of the neonates varied from 2,186 g to 4,000 g. Furthermore, the average age of neonates varied from 2 days to 9 days. Four doses of clofibrate (25, 30, 50, 100 mg/kg of neonatal body weight) were used. The bilirubin level of neonates significantly decreased in the intervention group 24, 36, 48, and 72 hours after the start of treatment. Clofibrate administration decreased total serum bilirubin, especially from the second day onwards, and also reduced hospitalization time, hospital costs, and side effects from hospitalization.