The objective of the present study is to prepare bio silica nanoparticles (SN) from rice husks as a biomass agricultural solid waste material. The synthesized silica nanoparticle was investigated with different tools such as TGA, XRD, SEM, TEM, nitrogen gas adsorption, and FTIR. Adsorption of amoxicillin was studied under different application conditions such as the effect of dosage of adsorbent, medium acidity, time of shaking, initial amoxicillin concentration, and the effect of temperature. Characterization techniques showed that SN is characterized by a high surface area (529.2 m2/g), small pore radius (1.32 nm), thermal stability, and particle size within range of 20–25 nm as calculated from TEM analysis. Adsorption of amoxicillin onto SN followed PSO kinetic models and well fitted with Temkin, van ‘t Hoff, and Langmuir linear models with maximum adsorption capacity reached 99.8 mg/g at 38 °C. The adsorption process is endothermic and spontaneous, as shown by thermodynamic characteristics. Desorption and reusability studies confirmed that acetone is the most efficient desorbing agent with 97.1% desorption efficiency. While reusability of solid adsorbent after six cycles of adsorption and desorption of amoxicillin is reduced by only 7.1%.