<p>Nanozymes, particularly those demonstrating high peroxidase-like activities, have emerged as innovative alternatives to conventional antibiotics. This paper reports on the enhancement of intrinsic peroxidase mimetic activity of a highly stable Au@Pt-TiO₂ nanocomposite under ultrasound stimulus. The bimetallic Au@Pt-TiO₂ nanocomposite was synthesized through a one-pot solvothermal chemical process. It was characterized by using X-ray powder diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), X-ray fluorescence (XRF) techniques. Surface modification with polyethylene glycol (PEG) provided the nanocomposite with water solubility, biocompatibility, and functionalization, crucial for its biomedical utility. The peroxidase-like activity of the nanocomposite was examined either without or with external ultrasound stimulus. We evaluate the oxidation of O-phenylenediamine (OPD) to assess its oxidative efficiency. Additionally, the catalase activity of this nanocomposite was studied. Notably, under ultrasound stimulus, designed to mimic clinical sonodynamic therapy (SDT) conditions, the Au@Pt-TiO₂ nanocomposite exhibited an enhanced intrinsic peroxidase activity. Furthermore, we investigate the sono-thermal effects of the Au@Pt-TiO₂ nanocomposite. Our results indicate that the heightened intrinsic peroxidase activity under ultrasound stimulus holds significant promise for the development of efficient therapeutic nanoplatforms in medical applications, particularly in the fields of SDT by enhancing the production of reactive oxygen species (ROS).</p> Graphical Abstract <p></p>