Developing bioactive materials with multifunctional properties is crucial for enhancing their biomedical applications in regenerative medicine. Bioactive glass nanoparticle (BGN) is a new generation of biomaterials that demonstrate high biocompatibility and tissue-inducing capacity. However, the hard nanoparticle surface and single surface property limited their wide biomedical applications. In recent years, the surface functional strategy has been employed to decorate the BGN and improve its biomedical applications in bone tissue repair, bioimaging, tumor therapy and wound repair. This review summarizes the progress of surface-interface design strategy, customized multifunctional properties and biomedical applications in detail. We also discussed the current challenges and further development of multifunctional BGN to meet the requirements of various biomedical applications.