Triple-negative breast cancer (TNBC) has aggressive characteristics as exemplified by the high risk of recurrence, metastasis, andpatientmortality. Cytotoxicchemotherapy may reduce tumor burden initially, but leave behind chemo-resistant breast cancer stem cells (BCSCs) that lead to tumor recurrence and metastasis. Chemotherapy induces BCSC enrichment through the activation of glutathione biosynthesis pathways, which increases intracellular glutathione levels and specifies the BCSC phenotype through complicated downstream signaling pathways. Glutathione S-transferases (GSTs), a superfamily (which contains seven cytosolic classes: Alpha, Kappa, Mu, Omega, Pi, Theta, and Zeta, and one microsomal class MGSTs) of phase II enzymes that catalyze the conjugation of glutathione with electrophilic compounds, play a critical role in detoxification and chemotherapy resistance of cancer cells. However, the role of GSTs in the regulation of BCSCs is largely elusive. In the present study, we first investigated the expression of all GST family members in response to chemotherapeutic drug carboplatin treatment at the dose of IC₅₀ in multiple TNBC cell lines, and found four members of the GST Mu family (GSTM1, GSTM2, GSTM3, and GSTM4) were markedly repressed in all four cell lines. GSTM1/2/3/4 mRNA and protein were also repressed by other FDA-approved chemotherapy drugs paclitaxel and gemcitabine at the dose of IC₅₀ in TNBC cell lines. Carboplatin also repressed GSTM1/2/3/4 expression in vivo, as shown in SCID (severe combined immunodeficiency) mice transplanted with MDA-MB-231 cells and in MMTV-PyMT transgenic mice (a genetically engineered autochthonous breast cancer model) that were treated by carboplatin.