Dill, a small annual herb, is widely used as a flavoring agent in dishes including salads. It has been demonstrated that dill extract and its essential oil show hypolipidemic effects in rats. However, the mechanism of these effects has not been elucidated yet. We found that dill seed extract (DSE) activated peroxisome proliferator-activated receptor-α (PPAR-α), an indispensable regulator for hepatic lipid metabolism, by luciferase assay. Thus, we performed DSE feeding experiments using diabetic obese model KK-Ay mice to examine the effects of DSE on PPAR-α activation in vivo. A 4-week feeding of DSE contained in a high-fat diet decreased plasma triacylglyceride and glucose levels and increased the mRNA expression levels of fatty acid oxidation-related genes in the liver. In addition, the DSE feeding as well as bezafibrate (a PPAR-α potent agonist) feeding increased oxygen consumption rate and rectal temperature. These results indicate that DSE suppresses high-fat diet-induced hyperlipidemia through hepatic PPAR-α activation.