Micron and submicron scale artificial silica spheres were used to quantitatively detect the ultrasonic cleaning procedure for an ultrasmooth optical substrate. Silica spheres with sizes from 1 to 3 μm were explored to efficiently reduce the ultrasonic power for ultrasonic frequencies of 40, 80, and 120 kHz. On account of submicron silica spheres with sizes from 0.3 to 1.0 μm, the cleaning efficiencies for the ultrasonic frequencies of 170, 220, and 270 kHz were quantity evaluated, and the removal efficiency was effectively increased by employing a solution of NH4OH, H2O2, and deionized water with an optimized configuration. Furthermore, for the range from 40 to 270 kHz, according to investigations of the ultrasonic time, the particles’ removal process was explored during the ultrasonic treatments, and the damages of ultrasound on the ultrasmooth substrate within the ultrasonic time were also detected. The quantitative results give us many clues for realizing the optimization of an ultrasonic cleaning procedure for ultrasmooth optical substrates.