In this study, we first analyzed the disease incidence of different disease-resistant P. pratensis varieties, and then investigated changes in their in vivo redox states. Isobaric tags for relative and absolute (iTRAQ) proteomics and nontargeted metabolomics were utilized to elucidate the response mechanism of P. pratensis to powdery mildew infestation. We comprehensively analyzed the shared KEGG pathways of DAPs and DEMs and ultimately identified four shared KEGG pathways. Among these pathways, the phenylpropanoid biosynthesis pathway, which is enriched in both P. pratensis varieties, was selected for further analysis. Further analysis revealed that lignin biosynthesis plays an important role in P. pratensis response to powdery mildew infestation.