Halloysite nanotubes (HNTs) are naturally aluminosilicate clay minerals that have the benefits of large surface areas, high mechanical properties, easy functionalization, and high biocompatibility, HNTs have been developed as multifunctional nanoplatforms for various bioapplications. Although some reviews have summarized the properties and bioapplications of HNTs, it remains unclear how to functionalize the modifications of HNTs for their personalized bioapplications. In this review, based on the physicochemical properties of HNTs, we summarized the methods of functionalized modifications (surface modification and structure modification) on HNTs. Also, we highlighted their personalized bioapplications (anti-bacterial, anti-inflammatory, wound healing, cancer theranostics, bone regenerative, and biosensing) by stressing on the main roles of HNTs. Finally, we provide perspectives on the future of functionalized modifications of HNTs for docking specific biological applications.