This study evaluates the modulation of inflammatory markers by petroleum ether fraction of Trigonella foenum-graecum L. (PE-TFG) seed extract in ovariectomized rats. The HPTLC method was used for standardization and to quantify the diosgenin in PE-TFG. For testing PE-TFG in rats, the total duration of treatment was 12-weeks, and the rats were sacrificed on week 12. The tissue samples such as blood, liver, heart, and aorta were isolated for testing inflammatory markers such as adiponectin, leptin, PPAR-γ, TNF-α, lipid profile, hepatic markers, antioxidants, and oxidative stress markers. The PE-TFG treatment decreased the elevation of total cholesterol, triglyceride, AST, and ALT. Upon PE-TFG treatment, there was a significant increase in adiponectin and PPAR-γ mRNA expression. Leptin and TNF-α were normal after treatment with PE-TFG seed extract. Further, micro-steatosis of hepatocytes marked glomerular hypertrophy in the kidney and increased thickness of tunica intima and media of common carotid artery was reversed after treatment with PE-TFG. PRACTICAL APPLICATIONS: Trigonella foenum-graecum L. is a curative plant used to treat inflammatory conditions like diabetes, obesity, dyslipidemia, arthritis, cancer, and digestive disorders. In our study, PE-TFG supplementation has a protective effect on OVX-induced inflammation, oxidative stress, mRNA expression of adiponectin and PPAR-γ, hepatic steatosis, and decreased thickness of tunica intima and media of common carotid artery.