Abstract: Polyethylene terephthalate microplastics (PET-MPs), pervasive environmental contaminants, are suspected of exerting neurotoxic effects on the central nervous system (CNS). Nevertheless, the precise molecular mechanisms underpinning PET-MP-induced CNS injury are yet to be elucidated. This investigation utilized a network toxicology framework to systematically dissect the potential targets and molecular pathways implicated in PET-MP-induced Alzheimer's disease (AD). The structural data for PET-MPs were sourced from PubChem, while their prospective biological targets were predicted using the ChEMBL, SEA, and Swiss Target Prediction databases. Concurrently, AD-associated targets were curated from GeneCards, OMIM, and TTD. Intersection analysis identified common targets, which were then used to construct a protein-protein interaction (PPI) network via the STRING database. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, were executed using the "clusterProfiler" package in R. Finally, molecular docking simulations with CB-Dock2 were performed to assess the binding affinity between PET-MPs and key targets. Our analysis identified 690 potential targets of PET-MPs and 4278 targets associated with AD, revealing 312 overlapping targets. Within the PPI network, 144 core targets, including EGFR, SRC, SHC1, and CCL5, were prioritized. GO analysis indicated that these targets are predominantly involved in biological processes such as leukocyte migration and chemotaxis, are localized to cellular components like the vesicle lumen and external plasma membrane, and possess molecular functions related to kinase activity and chemokine binding. KEGG pathway analysis highlighted significant enrichment in the PI3K-Akt and MAPK signaling pathways. Molecular docking results validated a stable binding potential, with binding energies for PET-MPs with EGFR, SRC, SHC1, and CCL5 all being lower than −5 kcal/mol. This research offers novel theoretical insights into the neurotoxicity of PET microplastics and provides a scientific foundation for guiding environmental risk management and formulating targeted therapeutic interventions for Alzheimer's disease.