Glioblastoma is the most common brain cancer in adults and presents a major challenge for targeted drug delivery due to the blood-brain barrier (BBB) and the highly infiltrative growth of the glioma cells into the brain. Cell-mediated drug-delivery systems have been proposed as a potential strategy to enhance the effects of drugs and reduce their side effects in the treatment of cancer. Neutrophils are the most abundant type of WBC in humans and can overcome impermeable barriers and transport drugs into inflamed sites such as tumors. Therefore, a promising approach for an innovative drug delivery system is the use of neutrophils as Trojan horses for drug delivery. However, compared to other leukocytes such as macrophages, little is known about how human neutrophils respond to and take up synthetic particles. In this review, we summarize the factors affecting the uptake of nanoparticles (NPs) by neutrophils, as well as recent advances and challenges related to the interaction between neutrophils and NPs, with particular emphasis on the interaction of magnetic mesoporous silica NPs, liposomes, albumin NPs, and PLGA NPs with neutrophils. Finally, the potential application of neutrophil-based drug delivery systems for the prevention of glioblastoma recurrence and also the potential application of neutrophil-mimicking nanoparticles (NM-NPs) in glioblastoma therapy are discussed.