The disassembly and eliminating the amyloid-β (Aβ) aggregates has become an effective way to treat Alzheimer's disease (AD). Herein, for the first time, the near-infrared (NIR) activated silicene nanosheets (SNSs) have been identified as an effective nontoxic photothermal conversion agent for irreversibly disassembly of the Aβ_33–42 aggregates. The SNSs synthesized by a combination of mild oxidation method and liquid exfoliation method possess good biocompatibility and biodegradability, and high near-infrared photothermal conversion capabilities. Under NIR light, the SNSs could disassemble the large and dense Aβ_33–42 mature fibrils into short fibrils and even form thin films, leading to the degradation rate of 96.47%. The circular dichroism spectrum, fluorescent spectra, and nanostructure were analyzed to monitor the photothermal degradation of mature Aβ_33–42 fibrils for elaborating the mechanism beneath. This study might provide a clue for developing potential therapeutic strategy for AD and related neurodegenerative diseases.