In this study, halloysites, one of the most abundant clays, with hollow nanotube features were reconstructed by selectively etching silica from the outermost layer of the halloysites associated with unzipping the nanotubes to nanosheets via ball milling, and then, nickel nanoparticles were confined by the resulting defects in the nanosheets to boost charge transfer by a wet impregnation method. The obtained materials were developed as coke-resistant defect-confined Ni-based nanosheet-like catalysts for CO2 reforming of methane (CRM) for the first time. The as-prepared catalyst exhibited good coke and sintering resistance performance in CRM, and especially, there was almost no loss of activity even after a 20 h stability test due to the strong interaction between the Ni nanoparticles and the support. The present investigations may provide a new pathway for the design and application of highly coke-resistant CRM catalysts.