To examine the serum triglyceride (TG)-lowering effect of a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), and its mechanisms, we carried out a G-hesperidin administration test in hypertriglyceridemic subjects. G-Hesperidin was administered to the subjects at 500 mg/d for 24 wk. In this study, the subjects were classified into highTG type (TG>150 mg/dL), borderline-TG type (TG 110-150mg/dL) and normal-TG type (TG<110 mg/dL) on the basis of their initial serum TG values. Among these phenotypes, serum TG level significantly decreased in the high-TG type during the G-hesperidin administration period. It was also observed that elevated values of serum remnant-like particle cholesterol (RLP-C), apolipoprotein (apo) B, apo C-II, apo C-III and apo E occurred in the high-TG type and that these serum levels were significantly reduced by G-hesperidin administration. Moreover, polyacrylamide gel electrophoresis analysis of serum lipoproteins revealed that the very low-density lipoprotein (VLDL)/low-density lipoprotein (LDL) ratio and LDL migration index of the high-TG type were remarkably higher than those of the other phenotypes but that their high values were significantly reduced by the administration. These results indicate that G-hesperidin preferentially lowers serum TG in hypertriglyceridemic subjects and that this effect is possibly caused by the improvement of VLDL metabolic abnormality, leading to the reduction of small dense LDL.