The basic properties of herbal medicines are cold, hot, warm, and cool. The differentiation of these properties is important for the diagnosis and treatment of diseases. Ginseng and American ginseng possess opposite properties of warm and cool, respectively. At present, the mechanisms and the influence of steaming leading to the differences in their properties are not clear and require further investigation. Therefore, nontargeted metabonomics based on liquid chromatography-mass spectrometry was applied to investigate the effects of ginseng, American ginseng, and their variants on the changes in endogenous metabolites in rat urine. A total of 19 potential biomarkers were screened out and identified, of which 17, 7, and 5, were respectively related to warm, cool, and both warm and cool properties with opposite effects. The metabolic pathways corresponded to fatty acids, lipids, glycolysis, and energy metabolisms. The warm and tonic effects of red ginseng are stronger than those of ginseng and consistent with the theory of traditional Chinese medicine. The red American ginseng has cool property; however, the degree of coolness is less than that of American ginseng. This study provides a reference methodology to understand the effects of processing and mechanisms associated with the differences in the properties of herbal medicines.