While a hexahistidine affinity tag can be introduced at protein termini or internal sites by standard molecular biology procedures for purification, immobilization, or labeling of proteins, here the versatility of this concept is exploited for the chemical preparation of novel hexahistidine-tagged single-walled carbon nanotubes (His6-tagSWNTs), a novel hard template useful for solubilizing, assembling, processing, and interfacing SWNTs in aqueous conditions. Water-soluble and exfoliated His6-tagSWNTs are prepared and fully characterized. This functional molecular module is able to interact via robust physisorption (π−π stacking) with the sidewall of SWNTs and combines the versatility of small, water-soluble reporters (His6) for hierarchical directed self-assembly (HDSA) and construction of nanocomposites. It is demonstrated that metal coordination bonds with Ni(II) can be used for the supramolecular self assembly of His6-tagSWNTs, generating complex reticulated networks and architectures. The His6-tagSWNTs hard template nanohybrid is further utilized for directed self-assembly with silica nanoparticles. The versatility of the novel hybrids opens a new era for the rational design, smart (bio)functionalization, processing, interfacing, and self assembling of carbon nanotubes for the construction of multicomposites and more complex systems with controllable spatial organization and programmable properties for a wide range of applications in biology, nanoelectronics, and catalysis.