This study investigates the toxic effects of the environmental contaminant triclosan (TCS) on porcine oocyte meiosis and the protective role of melatonin (MT). Using an in vitro maturation model, TCS was found to impair polar body extrusion and cumulus expansion, while inducing oxidative stress, mitochondrial and endoplasmic reticulum dysfunction, and apoptosis. To explore the underlying molecular mechanisms, we performed proteomic profiling using a Bruker timsTOF Pro2 mass spectrometer with a Direct DIA acquisition strategy. Differentially expressed proteins (DEPs) were quantified and analyzed using Spectronaut software, followed by functional annotation and enrichment analysis via GO, KEGG, and Reactome databases. The results revealed that the p53 signaling pathway plays a central role in both TCS-induced toxicity and MT-mediated rescue, providing new insights into reproductive damage caused by environmental pollutants.