<p>The aim of this study is to evaluate the therapeutic effects of <i>Scutellaria baicalensis</i> total flavonoids (STF) in a rat model of metabolic syndrome (MS), with particular focus on the core regulatory mechanisms contributing to metabolic homeostasis. Additionally, the modulation of peroxisome proliferator-activated receptors (PPARs) by STF was investigated to elucidate its molecular targets and associated features within the pathophysiology of MS. Metabolic syndrome was induced in Sprague Dawley rats through the administration of a high-fat/high-glucose diet combined with streptozotocin (STZ). STF was administered orally during the induction period. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and fasting insulin (FINS) were quantified. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Hepatic concentrations of TC and TG were also measured. Histopathological alterations were evaluated using hematoxylin and eosin (HE) staining, while hepatic lipid accumulation was assessed through Oil Red O staining. Hepatic expression levels of PPARα and PPARγ proteins were determined via Western blot analysis. Treatment with STF at doses of 50 and 100&#xa0;mg·kg⁻¹ significantly reduced serum levels of TC, TG, LDL-C, FBG, FINS, and HOMA-IR, while preventing the decline in HDL-C levels among rats with MS. STF administration also alleviated abnormal liver weight and suppressed hepatic accumulation of TC and TG, accompanied by improvements in histological features. Western blot analysis revealed upregulation of hepatic PPARα and PPARγ protein expression following STF treatment. STF demonstrated the capacity to reduce body weight and improve lipid profiles and insulin resistance in rats with MS. These effects may be associated with the regulation of PPARα and PPARγ protein expression.</p>