In this study, three formulations (F1, F2, and F3) were developed to fabricate hybrid scaffolds composed of chitosan (CS), polyvinylpyrrolidone (PVP), and polyvinyl alcohol (PVA), doped with curcumin (CUR) and silicon dioxide nanoparticles (NPs-SiO₂). Structural analysis of the scaffolds was performed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). This analysis demonstrated that incorporating bioactive molecules, such as curcumin (CUR) and silicon dioxide nanoparticles (NPs-SiO₂), modified intermolecular interactions within the prepared scaffolds, thereby favoring the formation of more stable amorphous structures. This effect was most evident in scaffold formulation 3, which exhibited a more porous architecture with a uniform distribution of NPs-SiO₂. Furthermore, mechanical evaluation of the formulations revealed that F2 exhibited the highest elastic modulus (0.773 ± 0.177 MPa) and compressive strength (1.015 ± 0.012 MPa), while F3 showed a more balanced combination of flexibility, structural stability, and displacement capacity. All formulations achieved complete inhibition of the Gram-positive and Gram-negative bacterial strains evaluated under the same test conditions. In vitro studies demonstrated that F3 maintained cell viability above 80% in normal BHK-21 fibroblasts while exhibiting enhanced cytotoxicity toward HEp-2 tumor cells (IC₅₀ = 373.6 µg/mL). Additionally, subdermal implantation revealed the presence of trabeculae-like structures, osteocyte-like lacunae, and osteoblastic-like cells in F3, suggesting the initiation of osteogenic-type tissue organization. These findings identify F3 as the formulation with the most favorable balance of structural, mechanical, antimicrobial, and biological properties, supporting its potential application as a multifunctional scaffold for tissue regeneration.