We detected that TMZ/siPD‐L1@GLPN/dsb can simultaneously deliver large amounts of TMZ and si‐PD‐L1 to TMZ‐resistant orthotopic GBM tissues by inhibiting PD‐L1 protein expression, increasing the percentage of CD3+CD8+IFN‐γ+cells (Teff cells) and reducing the percentage of CD4+CD25+FoxP3+ cells (Treg cells) in the orthotopic TMZ‐resistant GBM tissues. Here, FOXP3 is linked to glioblastoma.