This study analyzed mechanism of saponins regulating fatty alcohol oxidase (FAO) to reduce myocardial remodeling and control heart failure. 30 Sprague-Dawley (SD) rats were randomly and equally assigned into control group, model group, and saponin group, followed by analysis of myocardial tissue pathology, cyclic guanosine monophosphate (cGMP), Recombinant Hman Protein (PKG), Peroxisome proliferator-activated IP: 20 8 10920 On Sun 18 Jun 2023 10:1 :01 receptors (PPAR-a) expression levels, and cell apoptosis. Compared to control group, cGMP, PKG, PPAR-a, Copyright: American Sc entific Pub ishers uncoupling protein 3 (UCP3), and cluster of differntiation 36 (CD36) mRNA levels in the model group were Delivered by Ingenta significantly decreased (P < 0.001) and elevated in the saponin group (P < 0.05). Oxidation rates of adenosine triphosphate (ATP), phosphocreatine/ATP, and palmitic acid in the model group were significantly decreased (P < 0.001) and elevated in the saponin group (P < 0.05). Apoptosis and level of Cleaved caspase-3 were significantly reduced in the model group (P < 0.001) and increased in the saponin group (P < 0.05). Levels of cGMP, PKG, PPAR-a, UCP3 and CD36 in the model group decreased (P < 0.001) and increased in the saponin group (P < 0.001), but lower than in the control group. Relative to the model group, Brain Natriuretic Peptide (BNP) level was significantly increased in the inhibitor group and decreased in the agonist group (P < 0.001). Saponins activate cGMP-PKG signaling pathway, up-regulating cGMP and PKG, promoting PPAR-a expression, inhibiting myocardial cell necroptosis, thereby reducing inflammatory infiltration of myocardial cells, improving connective tissue hyperplasia, and reducing myocardial injury and myocardial remodeling, thus play an anti-heart failure role.