Jujube is an important medicinal plant and economic crop in China. However, long-term infestation by jujube witches’ broom disease has led to significant yield losses. In this study, TMT-based quantitative proteomics was employed to investigate the molecular mechanisms underlying disease resistance. Our results revealed that differentially expressed proteins were predominantly localized in the cytoplasm and chloroplasts, which function synergistically to maintain cellular homeostasis. Chloroplasts generate ATP and NADPH through photosynthesis, supplying energy and reducing power for various metabolic activities, while cytoplasmic pathways such as glycolysis and the tricarboxylic acid cycle provide essential precursor substances for chloroplast-based photosynthetic processes. These findings demonstrate the coordinated regulation of energy metabolism at the subcellular level, offering a theoretical foundation for the identification and screening of disease-resistant proteins.