In the present study, a bimetallic nanostructure of gold-copper (Au-CuNPs) was decorated on the surface of porous silicon (PSi) using an easy galvanic replacement reaction between metal ions and PSi in the presence of 0.1 M hydrofluoric acid solution. The morphology and structures of the Au-CuNPs@PSi nanocomposite were characterized using X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE-SEM), fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) energy-dispersive X-ray spectroscopy (EDX) and cyclic voltammetry (CV) techniques. Then, prepared nanocomposite was used as a modifier in screen-printed carbon electrode (SPCE) for the highly sensitive simultaneous determination of codeine (COD) and acetaminophen (ACE). The combination of PSi and metals nanoparticles provide a porous and high surface area with excellent electrical conductivity which leads to reduce the peak potentials and enhance the oxidation peak currents of COD and ACE at the surface of the Au-CuNPs@PSi/SPCE nanosensor. The dynamic linear ranges were obtained from 0.06 to 0.6 µM for both COD and ACE and the detection limits (3.0 S/N) estimated 0.35 µM for COD and 0.30 µM for ACE, respectively. Moreover, recovery tests were carried out in real samples such as urine, human blood plasma, and tablets.