This review discusses the use of peptide-functionalized nanoparticles (NPs) for the treatment of glioblastoma (GBM), a highly aggressive brain tumor. The blood-brain barrier (BBB) and tumor heterogeneity pose significant challenges to effective treatment, but NPs can overcome these obstacles by attaching targeting ligands, with peptides being particularly effective due to their ease of synthesis and high selectivity. The article critically reviews single and multiligand strategies, highlighting other approaches such as external stimuli, biomimetic methods, and nanocatalytic medicine, which show significant potential in GBM treatment. It also discusses alternative routes of administration, including nose-to-brain delivery and local treatment within the resected tumor cavity. The review emphasizes the importance of overcoming challenges in developing efficient therapeutic drug delivery systems for GBM. Key receptors exploited for targeting GBM include the low-density lipoprotein receptor (LDLR), transferrin receptor (TfR), neuropilin-1 (NRP-1), interleukin-13 receptor alpha 2 (IL-13Ra2), integrin receptors, and others. Peptides such as Angiopep-2 (ANG2), transferrin, tLyp-1, and RAP12 have been used to target these receptors, enhancing BBB penetration and GBM cell targeting. Cell-penetrating peptides (CPPs) are also discussed, as they can transduce cell membranes and improve drug delivery to GBM cells. Multiligand strategies, which combine multiple targeting ligands, offer enhanced precision and efficiency in targeting GBM cells and stem cells. Additionally, the integration of external stimuli, such as magnetic fields, hyperthermia, and photothermal therapy, with peptide-functionalized NPs is explored, demonstrating their potential to improve GBM treatment outcomes. The review concludes that peptide-functionalized NPs represent a promising approach for the development of more effective therapies for GBM.This review discusses the use of peptide-functionalized nanoparticles (NPs) for the treatment of glioblastoma (GBM), a highly aggressive brain tumor. The blood-brain barrier (BBB) and tumor heterogeneity pose significant challenges to effective treatment, but NPs can overcome these obstacles by attaching targeting ligands, with peptides being particularly effective due to their ease of synthesis and high selectivity. The article critically reviews single and multiligand strategies, highlighting other approaches such as external stimuli, biomimetic methods, and nanocatalytic medicine, which show significant potential in GBM treatment. It also discusses alternative routes of administration, including nose-to-brain delivery and local treatment within the resected tumor cavity. The review emphasizes the importance of overcoming challenges in developing efficient therapeutic drug delivery systems for GBM. Key receptors exploited for targeting GBM include the low-density lipoprotein receptor (LDLR), transferrin receptor (TfR), neuropilin-1 (NRP-1), interleukin-13 receptor alpha 2 (IL-13Ra2), integrin receptors, and others. Peptides such as Angiopep-2 (ANG2), transferrin, tLyp-1, and RAP12 have been used to target these receptors, enhancing BBB penetration and GBM cell targeting. Cell-penetrating peptides (CPPs) are also discussed, as they can transduce cell membranes and improve drug delivery to GBM cells. Multiligand strategies, which combine multiple targeting ligands, offer enhanced precision and efficiency in targeting GBM cells and stem cells. Additionally, the integration of external stimuli, such as magnetic fields, hyperthermia, and photothermal therapy, with peptide-functionalized NPs is explored, demonstrating their potential to improve GBM treatment outcomes. The review concludes that peptide-functionalized NPs represent a promising approach for the development of more effective therapies for GBM.