Although hesperidin lowers serum total cholesterol (TC) or triglyceride (TG) in animal models, its effect in humans remains unclear. Using a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), as a hesperidin source, we examined the efficacy on hyperlipidemic subjects. G-Hesperidin was administered to the subjects at 100 or 500 mg/d for 6 wk. The percentage of subjects who had a change in serum cholesterol levels was less than 20%. However, 45-55% of the total subjects showed a reduction in serum TG level. The subjects were classified into normal (TC<230mg/dL, TG<150mg/dL), high-TC (TC>230 mg/dL, TG<150 mg/dL) and high-TG (TG>150 mg/dL) types. While serum cholesterol levels scarcely changed in any phenotype, TG level was significantly reduced by administration in the high-TG type. In this phenotype, serum apolipoprotein (apo) C-II and E levels decreased by the administration, but non-apo B. G-Hesperidin also raised low-density lipoprotein (LDL)-cholesterol/apo B in the high-TG type. These results indicate that G-hesperidin preferentially lowers serum TG in hypertriglyceridemic subjects and that this effect is possibly caused by the facilitation of catabolism of TG-rich lipoproteins and may contribute to the reduction of small dense LDL.