Obesity and overweight contribute significantly to the burden of chronic diseases and complications globally. The rising prevalence of these conditions in Nigeria, especially among middle-class workers has been attributed to the acculturation of Western dietary patterns, reduced intake of dietary fibre, and sedentary lifestyles. Considering the risks associated with obesity and the associated side effects of orthodox medicine, a lot of studies have been dedicated to finding alternative treatments with limited side effects that are affordable hence, the use of medicinal plants such as Vernonia amygdalina. This study examined the therapeutic effects of V. amygdalina aqueous leaf extract on the biomarkers of metabolic syndrome in high-fat diet (HFD)-induced obese rats. 30 male Wistar rats were obtained and divided randomly into five groups containing six rats each. Group A was fed with only normal rat chow, while a high-fat diet was fed to groups B, C, D and E with V. amygdalina extract fed to groups C, D, and E alone after the induction of obesity. The animals were sacrificed on the 28th day and various analyses including growth performance, the concentration of blood glucose, serum lipid profile, and renal and hepatic function tests were performed. The group fed with only HFD had significantly high body weight, blood glucose concentration, serum levels of cholesterol, triglycerides, and liver and kidney biomarkers. However, posttreatment of groups C, D, and E with an aqueous extract of V. amygdalina significantly reduced these biomarkers to physiological levels and the organ tissue structure showed improvement. Thus, indicating the anti-obesity effects and the continuous role of V. amygdalina in weight loss management and prevention of obesity.