Supra-amphiphiles assembled by macrocycle-based host–guest interactions have received considerableattention in recent years due to their dynamic properties and wide applications. Pillar[n]arenes are aunique family of macrocycles which exhibit outstanding host–guest behavior. Developing water-solublepillar[n]arene (WP[n]) based supra-amphiphiles is an effective way to introduce this special macrocycleinto  functional  nanomaterials  through  controlled  self-assembly.  Specifically,  WP[n]-based  supra-amphiphiles can further form different nanomaterials, such as micelles, vesicles, and other types ofnanoparticles (NPs), which may become good candidates for nanocarriers of payloads. Herein, wehighlight recent significant achievements in functional nanocarriers fabricated from supra-amphiphilesbased on WP[n]s. By showing a series of examples, the preparation strategies, characterization, andstimuli-responsive behaviors of these nano-sized assemblies based on WP[n] derivatives are described.Furthermore, some important applications of WP[n]-based nanocarriers, such as drug/gene/proteindelivery, photodynamic/photothermal therapy, and optical materials, are discussed in detail. Finally,future challenges and research directions in this rapidly evolving field are outlined.