Every year, metabolic syndrome and cardiorenal diseases cause many deaths worldwide. African bitter leaf (Vernonia amygdalina L.) is known for its numerous therapeutic effects. Potentially, it can lower plasma lipid and glucose levels, which, in turn, may improve the condition of patients with the abovementioned diseases. This research featured the antihyperlipidemic and antihyperglycemic effects of methanol extract of V. amygdalina in an animal model of metabolic syndrome. Twenty albino rats were divided into four groups. Groups A to C were orally administered with ghee (3 mL/kg) + high-cholesterol diet (500 mg/kg) + high-sugar diet (10 mL/kg) to induce metabolic syndrome. Group A served as negative control and received no treatment with bitter leaf methanol extract. Groups B and C received 200 and 400 mg/kg of V. amygdalina methanol extract, respectively. Group D received no administration. The cardiorenal injuries and alterations in blood lipids and sugar levels wereassessed via various biochemical analyses. The combination of ghee + high-cholesterol diet + high-sugar diet triggered a significant elevation of creatine kinase myocardial band, lactate dehydrogenase, aspartate aminotransferase, triglycerides, total cholesterol, low density lipoprotein-cholesterol, glucose, urea, creatinine, and potassium levels. The histopathological results agreed with the biochemical findings. However, the treatment with 200 and 400 mg/kg of V. amygdalina methanol extract was able to inhibit the adverse alterations causing a dosedependent significant antihyperlipidemic and antihyperglycemic effect (p < 0.05). Bitter leaf (V. amygdalina) demonstrated cardiorenal protective effects and may be used to manage metabolic syndrome.