Pterocarpus soyauxii (P. soyauxii) is a Fabaceae family traditionally used to treat menopausal disorders. This study aims to investigate the effect of P. soyauxii on menopause-related NAFLD and to determine its mechanisms of action and signaling pathways. In vitro experiments evaluated the antioxidant properties of P. soyauxii. In vivo studies using ovariectomized rat models underlined pathways and effects of P. soyauxii on biochemical and histological features linked with NAFLD. Findings suggest that P. soyauxii compounds are readily absorbed through the intestine and exhibit a relatively low level of toxicity. Protein-protein interaction, compounds target networks, and KEGG pathway analysis revealed several pathways and target proteins of P. soyauxii compounds. Indeed, they target specific proteins such as ERα/β, NADPH-O, EGFR, MAPK1, PPARα/G, and HMG-Co A reductase. Molecular docking revealed that P. soyauxii compounds demonstrate high binding affinity to various proteins. In vitro, P. soyauxii inhibits the oxidative power of OH, H2O2, and NO. In vivo, P. soyauxii significantly (p<
0.01, p<
0.001, and p<
0.01, respectively) reduces ALAT (25.14%), hepatic cholesterol (15.27%), and MDA (26.78%) levels at 200 mg/kg and prevents steatosis in the liver. These findings suggest that P. soyauxii may have a protective role against menopause-related NAFLD.