Silica nanoparticles were synthesized using the aqueous extract of orange peels by the green chemistry approach and simple method. The physicochemical properties such as optical and chemical banding of as-synthesized silica nanoparticles were analyzed with UV–visible spectroscopy and Fourier transform infrared spectroscopy. Scanning Electron Microscopy with Energy Dispersive X-Ray Analysis and X-ray diffraction analysis were employed to confirm the shape, size and elemental purities of the silica nanoparticles. The thermal stability and mass loss of the silica nanoparticles was examined using thermogravimetric analysis and zeta potential analysis. The surface plasmon resonance band of the silica nanoparticle was obtained in the wavelength of 292 nm. Silica nanoparticles with a spherical and amorphous nature and an average size of 20 nm were produced and confirmed by X-ray diffraction and Scanning Electron Microscopy. The zeta potential of the silica nanoparticles was −25.00 mV. The strong and broad bands were located at 457, 642 and 796 cm−1 in the Fourier transform infrared spectra of the silica nanoparticles, associated with the Si–O bond. All the results of the present investigation confirmed and proved that the green synthesized silica nanoparticles were highly stable, pure and spherical in nature. In addition, the antioxidant activity of the green synthesized orange peel extract mediated by the silica nanoparticles was investigated with a DPPH assay. The antioxidant assay revealed that the synthesized silica nanoparticles had good antioxidant activity. In the future, green synthesized silica nanoparticles may be used for the production of nano-medicine.