Glioblastoma (GBM) is the most aggressive and lethal type of primary brain tumor, characterized by its rapid growth, resistance to conventional therapies, and a highly immunosuppressive tumor microenvironment (TME). Recent studies have highlighted the critical role of neutrophils in the progression of GBM, where they contribute to tumor growth, invasion, and treatment resistance. As a result, neutrophils have emerged as a promising target for therapeutic intervention in GBM. Various strategies are being investigated to specifically target neutrophils within the GBM environment, including using small molecules, antibodies, and nanoparticle-based methods. These approaches aim to regulate neutrophils' recruitment, activation, and functions. This study reviews the latest findings regarding the involvement of neutrophils in GBM, explores potential techniques targeting neutrophils for therapeutic purposes, and discusses current clinical studies and prospects in this rapidly evolving field. By studying the diverse functions of neutrophils in GBM, these innovative therapeutic strategies can help address some of the most significant challenges in treating this malignancy.