Aim: To realize and characterize a new generation of keratin-coated gold nanoparticles (Ker-AuNPs) as highly efficient photosensitive nanosized therapeutics for plasmonic photothermal (PPT) therapy. Materials & methods: The chemical, physical, morphological and photothermal properties of Ker-AuNPs are investigated using dynamic light scattering, ζ-potential, UV–Visible, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, transmission electron microscopy and high-resolution thermography. In vitro experiments are performed on a human glioblastoma cell line (i.e., U87-MG), using viability assays, transmission electron microscopy, fluorescence microscopy, cytometric analyses and PPT experiments. Results: Experiments confirm the excellent biocompatibility of Ker-AuNPs, their efficient cellular uptake and localized photothermal heating capabilities. Conclusion: The reported structural and functional properties pointed out these Ker-AuNPs as a promising new tool in the field of biocompatible photothermal agents for PPT treatments against cancer-related diseases.