The prevalence of overweight-obesity and associated comorbidities have reached alarming levels necessitating the need to explore effective therapeutics. In the present work, we demonstrated the promising antiobesity activity of ethanolic fraction of Terminalia tomentosa bark (EFTT) in diet induced obese rat model. High Fat Diet (HFD)-fed obese rats were orally administered with EFTT (50, 100 and 200 mg/kg body weight). Changes in body weight, body composition, bone mineral concentration, bone mineral density, plasma glucose, insulin, leptin, adiponectin, circulatory and tissue lipid profiles, and the activities of liver antioxidant enzymes, key lipid metabolic enzymes and mRNA expressions of fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPAR-γ), leptin and tumor necrosis factor alpha (TNF-α) were assessed in experimental rats in the presence and absence of EFTT. At a dose of 200 mg/kg b.wt, EFTT has substantially attenuated body weight and related patho-physiological alterations in HFD-induced obese rats. These findings were correlated with histological observations of adipose tissue. The therapeutic activity of EFTT could be possibly through restoration of antioxidants status, regulation of key lipid metabolizing enzymes, expression of FAS, leptin, PPAR-γ and by synchronized control of energy metabolism in liver and adipose tissue.