The postprandial condition is recognized as a procoagulant state. Postprandial platelet hyperactivity plays a crucial role in the pathogenesis of metabolic syndrome. Botanical foods typically contain a multi-component composition derived from herbal practices. Therefore, it is difficult to determine which components regulate platelet hyperactivity. Metabolomic analysis is a valid and powerful tool with which to further define the mechanisms. We therefore aimed to assess the effect of Sanghuang-Danshen (SD) in the metabolome and clinical biomarkers on platelet hyperactivity after an acute challenge with high-lipid/glucose formula in healthy subjects. In a crossover randomized and placebo-controlled intervention study, fifty-six subjects received three doses of SD or placebo. Platelet aggregation and mRNA expression of cyclooxygenase-1 and vascular cell adhesion molecule-1 were all decreased in the SD group. SD administration appears to reduce the platelet hyperactivity associated with a postprandial condition. These changes are accompanied by alterations of the metabolomics. A total of 13 metabolites were found to be significantly different between placebo and the high-dose SD group, which were strongly involved in linoleic acid metabolism, alanine, aspartate and glutamate metabolism, arachidonic acid metabolism, and glycine, serine and threonine metabolism. By integrating components in SD, markers, and phenotype, we find that SD may modulate the platelet hyperactivity occurring in the postprandial state.