In this study, we performed a comprehensive proteomic analysis of mango leaves inoculated with the leaf spot pathogen A. alternata. Down-regulated proteins during pathogen invasion and colonization were primarily associated with photosynthesis, the phenylpropanoid and flavonoid biosynthesis pathways, and phenylalanine metabolism. In contrast, significantly up-regulated proteins were involved in tyrosine metabolism and the MAPK signaling pathway, highlighting their critical role in host resistance to the leaf spot pathogen. These findings provide valuable data on protein expression changes, offering potential targets for developing novel management strategies to enhance control of leaf spot disease.