Modified drug delivery systems (MDDSs) are valuable allies in the quest for optimizing pharmaceuticals, whether to modulate their release profiles or increase their bioavailability. In this context, silica particles in the nanometric size range stand out as excellent materials for MDDS applications, thanks to their favorable interactions with drugs provided by silanol groups. Experimental planning is a widely applied tool in various scientific fields, and in this study, its relevance is emphasized in the synthesis of silica nanoparticles as promising drug delivery systems. The research details the synthesis process of silica nanoparticles from diatomite using the sol-gel method, along with meticulous material characterization through analytical techniques such as X-ray diffraction (DRX), X-ray fluorescence (FRX), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (MEV), nitrogen adsorption/desorption (N2), dynamic light scattering (DLS), and zeta potential. Following the successful optimization of the synthesis, particles within the range of 292.5 ± 33.0 nm were obtained, with a yield of 90% and a polydispersity index of 0.218 ± 0.041. The experimental planning enabled the attainment of particles with appropriate size, high yield efficiency, and low polydispersity. The unique characteristics of silica particles, especially their favorable interactions with drugs due to silanol groups, point to notable potential in modulating drug release profiles and increasing their bioavailability. The incorporation of these modified release systems represents a significant advancement in the field of therapeutics, allowing for more effective and personalized approaches in the treatment of various diseases and medical conditions.