Hyperlipidemia and hypertension play a crucial role in the pathophysiology of endothelial dysfunction and the development, progression, and rupture of atherosclerotic plaque. Casticin (CAS) has direct anti-inflammatory effects by inhibiting multiple inflammatory signalling pathways. Our study aimed to evaluate CAS activity in an animal model of diet-induced hyperlipidemia. A total of 24 male rats were divided into 4 groups (n = 6): Group I was fed a standard diet, Group II was fed a high-fat diet (HFD), and Group III received HFD plus drug CAS (50 mg/kg) and Group IV group received control diet plus CAS drug. Lipid profile, atherogenic index, inflammatory, lipid metabolic enyzmes, cardiac markers, blood pressure, and oxidative stress markers were measured. Treatment with CAS significantly reversed this lipid profile, atherogenic index, cardiac lipid metabolic enzymes, cardiac markers and improved the antioxidant status in HFD-induced rats. In addition, CAS administration significantly reduced the inflammatory gene expression in cardiac tissues. The study suggested that CAS has strongly improved dyslipidemia, and reduces oxidative stress, inflammatory markers and blood pressure in rats fed with HFD.