Recent studies have shown that Panax ginseng has a variety of beneficial effects on the cardiovascular system. Homocysteine (Hcy), which is derived from methionine, has been closely associated with the increased risk of cardiovascular diseases. In the present study, whether the in-vivo long-term co-administration of ginseng total saponins (GTS), active ingredients of Panax ginseng, with L-methionine (Met) inhibits methionine-induced hyperhomocysteine (HHcy) and H-Hcy-induced cardiovascular dysfunctions was investigated, and it was found that the plasma Hcy level, which was measured after 30 and 60 days, in the GTS+Met co-administration group was more significantly reduced than in the Metalone-treatment group. The left-ventricle (LV) wall thickness of the heart was likewise examined in each treatment group, and it was found that the co-administration of GTS with Met significantly reduced the Met-induced LV wall thickness. The results of the study indicate that the in-vivo long-term co-administration of GTS with Met not only inhibited H-Hcy induced by long-term Met-alone administration but also attenuated the H-Hcy-induced cardiovascular dysfunctions in rats.