Prenatal exposure to valproic acid (VPA), an antiepileptic and mood-stabilizing drug, is a well-established environmental risk factor for autism spectrum disorder (ASD). To investigate region-specific molecular alterations, we performed tandem mass tag (TMT)-based quantitative proteomic profiling of the striatum in 9–10 week-old mice prenatally exposed to VPA and control littermates. Striatal tissues were processed by protein extraction, digestion, TMT labeling, and high-pH reversed-phase fractionation, followed by LC–MS/MS analysis on a Q-Exactive HF-X mass spectrometer. In total, 101 differentially expressed proteins (47 upregulated, 54 downregulated) were identified. Functional enrichment analysis implicated pathways related to synaptic transmission, neuronal development, oxidative stress response, and excitation/inhibition balance. Key down-regulated proteins included parvalbumin (PVALB), NR2F1, and metallothioneins (MT1, MT2, MT3), highlighting disrupted inhibitory signaling and metal ion homeostasis in VPA-exposed mice. This dataset provides comprehensive proteomic profiles of striatal tissue, supporting molecular insights into the mechanisms by which prenatal VPA exposure contributes to ASD-related phenotypes.