Introduction The blood–brain barrier (BBB) is a key obstacle to the delivery of drugs into the brain. Therefore, it is essential to develop an advanced drug delivery nanoplatform to solve this problem. We previously screened a small rabies virus glycoprotein 15 (RVG 15 ) peptide with 15 amino acids and observed that most of the RVG 15 -modified nanoparticles entered the brain within 1 h of administration. The high BBB penetrability gives RVG 15 great potential for brain-targeted drug delivery systems. Moreover, a multifunctional integrated nanoplatform with a high drug-loading capacity, tunable functionality, and controlled drug release is crucial for tumor treatment. Zeolitic imidazolate framework (ZIF-8) is a promising nanodrug delivery system. Methods Inspired by the biomimetic concept, we designed RVG 15 -coated biomimetic ZIF-8 nanoparticles (RVG 15 -PEG@DTX@ZIF-8) for docetaxel (DTX) delivery to achieve efficient glioblastoma elimination in mice. This bionic nanotherapeutic system was prepared by one-pot encapsulation, followed by coating with RVG 15 -PEG conjugates. The size, morphology, stability, drug-loading capacity, and release of RVG 15 -PEG@DTX@ZIF-8 were thoroughly investigated. Additionally, we performed in vitro evaluation, cell uptake capacity, BBB penetration, and anti-migratory ability. We also conducted an in vivo evaluation of the biodistribution and anti-glioma efficacy of this bionic nanotherapeutic system in a mouse mode. Results In vitro studies showed that, this bionic nanotherapeutic system exhibited excellent targeting efficiency and safety in HBMECs and C6 cells and high efficiency in crossing the BBB. Furthermore, the nanoparticles cause rapid DTX accumulation in the brain, allowing deeper penetration into glioma tumors. In vivo antitumor assay results indicated that RVG 15 -PEG@DTX@ZIF-8 significantly inhibited glioma growth and metastasis, thereby improving the survival of tumor-bearing mice. Conclusion Our study demonstrates that our bionic nanotherapeutic system using RVG 15 peptides is a promising and powerful tool for crossing the BBB and treating glioblastoma.