To date, the delivery of therapeutic agents for malignant brain tumors (such as glioblastoma multiforme (GBM)) remains a significant obstacle due to the existence of the blood-brain barrier (BBB). A multitude of delivery systems (hydrogels, micelles, polymeric nanoparticles, etc.) have been proposed, yet many of them exhibit limited tumor-specific inhibition effects. Herein, a drug-encapsulated dual-functionalized thermosensitive liposomal system (DOX@P1NS/TNC-FeLP) was developed for targeted delivery across the BBB. Specifically, a GBM-specific cell-penetrating peptide (P1NS) and an anti-GBM antibody (TN-C) were conjugated onto the liposome surface for targeted delivery. In addition, superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin (DOX) were co-loaded inside the liposomes to achieve thermo-triggered drug release when applying an alternating magnetic field (AMF). Results demonstrated that P1NS/TNC-FeLPs readily transported across an in vitro BBB model and displayed a thermo-responsive and GBM-specific cellular uptake as well as drug release profile. Additionally, results from immunofluorescent (IF) staining and RT-qPCR further demonstrated that DOX@P1NS/TNC-FeLPs specifically entered U-87 human GBM cells and suppressed tumor cell proliferation without causing any significant impact on healthy brain cell function. As such, the novel DOX@P1NS/TNC-FeLPs presented potent and precise anti-GBM capability and, therefore, are suggested here for the first time as a promising DDS to deliver therapeutic agents across the BBB for GBM treatment.