Combining diagnosis with therapy, magnetic iron oxide nanoparticles (INOPs) act as an important vehicle for drug delivery. However, poor biocompatibility of INOPs limits their application. To improve the shortcomings, various surface modifications have been developed, including small molecules coatings, polymers coatings, lipid coatings and lipopolymer coatings. These surface modifications facilitate iron nanoparticles to cross the blood-brain-barrier, which is essential for diagnosis and treatments of brain diseases. Here we focus on the characteristics of different coated INOPs and their application in brain disease, particularly gliomas, Alzheimer’s disease (AD) and Parkinson’s disease (PD). Moreover, we summarize the current progress and expect to provide help for future researches.