Due to at least 3 years of cultivation, Panax ginseng (ginseng) is susceptible to being attacked by pathogens which severely affect its quality and yield. Compared with other diseases of ginseng, Phytophthora blight caused by Phytophthora cactorum (P. cactorum) can spread rapidly and destroy almost the entire plant of ginseng, such as leaves, stems, and roots. However, little research was focused on this area, and how P. cactorum affected the metabolic profile of ginseng is still obscure. In the current study, we conducted a comprehensive analysis of metabolomics and transcriptomics to compare the differences in health and P. cactorum-affected ginseng leaves and stems. Metabolome analysis revealed that 110 and 113 significant differential metabolites were observably disturbed separately in ginseng leaves and stems. Transcriptome analysis demonstrated that 6424 and 9508 genes had remarkable variation in ginseng leaves and stems. Using conjoint analysis, we also revealed the changes in pathways “Alanine, aspartate and glutamate metabolism”, “Glycine, serine and threonine metabolism”, and “Biosynthesis of unsaturated fatty acids” and “Plant hormone signal transduction” in ginseng response to the P. cactorum. The current work provides an overview of the alteration of metabolic profile and gene expression profiles in ginseng leaves and stems in response to P. cactorum affection, which may help to further screen out the mechanism of plant-pathogen interaction at the molecular level.