<p>Calorie-rich diet (CRD) promotes obesity and metabolic dysfunction. <i>Kochia scoparia</i> seed infusion (KSSI) has demonstrated metabolic benefits. To investigate the effect of KSSI, administered in three different strengths, on the histopathological alterations associated with CRD-induced metabolic dysfunction in rats. Fifty male Wistar rats were assigned to five groups (n = 10 per group): Control, CRD, CRD + 1.5KSSI, CRD + 3KSSI, and CRD + 6KSSI. For ten weeks, control rats were fed a standard diet, the other groups—a CRD (rich in fat and fructose). KSSI was provided at increasing strengths as a drinking fluid to CRD + 1.5KSSI, CRD + 3KSSI, and CRD + 6KSSI groups. Serum triglycerides (TGs), fasting blood glucose and triglyceride-glucose (TyG) index were determined. At the end of the experiment, tissue samples from the liver, adipose tissue and coronaries were processed using hematoxylin and eosin staining. Hepatic steatosis and inflammation as well as coronary endothelial damage were evaluated semi-quantitatively. Adipocyte size was assessed quantitatively. CRD rats were characterized by increased serum TGs and TyG index (<i>p</i> &lt; 0.01), hepatic steatosis and inflammation (<i>p</i> &lt; 0.0001), adipocyte hypertrophy (<i>p</i> &lt; 0.001) and endothelial cell damage (<i>p</i> &lt; 0.0001) compared to the Control group. KSSI treatment significantly reduced the TyG index in CRD + 3KSSI group (<i>p</i> &lt; 0.01), the steatosis and inflammation in CRD + 3KSSI and CRD + 6KSSI groups (<i>p</i> &lt; 0.0001), restored adipocyte size in all treated groups (<i>p</i> &lt; 0.001) and attenuated the endothelial damage in CRD + 3KSSI (<i>p</i> &lt; 0.05) and in CRD + 6KSSI (<i>p</i> &lt; 0.0001) compared to CRD group. KSSI attenuated CRD-induced metabolic disturbances and exerted protective effects against hepatic steatosis and inflammation, adipocyte hypertrophy, and vascular endothelial damage.</p>