Polylactic acid (PLA) polymer has garnered significant attention due to its biocompatibility. The incorporation of copper oxide (Cu2O) nanoparticles into this polymer is expected to enhance its antibacterial, electrical, and thermal properties. This modification can potentially improve the performance of PLA in the fields of prosthetics manufacturing or printed circuit fabrication. However, the current research is rather focused on the mechanical properties of the PLA-Cu2O nanocomposites. This research is thus aimed to analyze PLA-Cu2O (97-3 wt%) nanocomposites with a double keyhole notch configuration both experimentally and numerically. Scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), X-ray mapping of elemental distribution(X-map), and thermogravimetric analysis (TGA) were employed to explore the morphology, crystallinity, homogeneity, purity, and thermal stability of the nanocomposite. The specimens were fabricated through two different processes: the classical method of compression molding and the innovative method of 3D printing. The results revealed the superior mechanical performance of the 3D-printed nanocomposite at a 0◦ raster angle, while the mechanical properties gradually decreased for raster angles of 45◦ and 90◦. The experimental test also indicated a decline in the maximum fracture load of specimens with a double keyhole notch and constant notch inclination angle by raising the notch radius. This behavior was also observed by increasing the notch inclination angle at constant notch radius. The numerical results were similar to the experimental findings. Moreover, the nanocomposite manufactured through the classical method exhibited higher critical fracture load compared to their 3D-printed counterparts with the same geometry.