Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic lipids, inflammation, and fibrosis. Currently, more than 110 phytochemical constituents of Passiflora edulis have been reported, which have been attributed with biological activities such as: antihypertensive, antidiabetic, antitumor, hepatoprotective, an-ti-inflammatory, and hypolipidemic. The objective of this study was to evaluate the in vitro and in silico effect of the ethanolic extract of P. edulis leaves on the transcriptional factors PPARα and SREBP-1. To this end, HepG2 cells were induced to an NAFLD model with oleic acid, the hepatic content of triglycerides and cholesterol was quantified both intracellularly and extracellularly, and protein-ligand molecular docking was performed to analyze the binding af-finities of some components of the extract with the human proteins PPARα and SREBP-1. The extract was found to reduce hepatic lipid content. Meanwhile, the molecular docking results showed that the bioactive components of the extract had a higher affinity for PPARα (agonist) than for SREBP-1c (antagonist). In conclusion, the results indicate the important role of P. edulis in the prevention and treatment of NAFLD.