Cisplatin is a platinum-based chemotherapeutic agent widely used to treat solid tumors; however, its clinical use is limited by severe neurotoxicity. Although cisplatin shows limited blood–brain barrier permeability, accumulating evidence indicates that it induces apoptosis-associated neurotoxicity in the central nervous system. In this study, we investigated cell type–specific apoptosis-associated responses of primary cortical neurons and glial cells to cisplatin. Cytotoxicity was evaluated in EMT6 murine mammary carcinoma cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the half-maximal inhibitory concentration (IC₅₀) was determined. This concentration was then applied to primary cortical cultures derived from postnatal day 0 Balb/C mice. Apoptosis-associated responses were assessed by Western blot analysis of BCL-2 expression and immunofluorescence staining of caspase-3. Cisplatin significantly reduced BCL-2 protein levels in primary cortical cultures (p<0.01). Immunofluorescence analysis further revealed a significant increase in caspase-3–positive neurons following cisplatin exposure (p<0.01), whereas no significant change was observed in GFAP-positive glial cells (p>0.05). These findings demonstrate that cisplatin induces cell type–specific apoptosis-associated responses in primary cortical cultures, with neurons showing greater vulnerability than glial cells, highlighting the importance of evaluating cisplatin-induced neurotoxicity in the central nervous system.