To design a controlled drug release preparation based on a safe natural material, a Konjac glucomannan (KGM) mixture containing 16.0 w/w% calcium hydroxide (Ca(OH)2) was ground in a planetary ball mill for 0–120 min. The mechanochemical effect on the physicochemical properties of the KGM ground product was investigated by Fourier-transform infrared spectroscopy (FT-IR), powder X-ray spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, and drug release testing. The FT-IR spectra of the ground KGM indicated that the deacetylation reaction of KGM was accelerated in the Ca(OH)2-containing sols by mechanochemical energy, and the degree of deacetylation of KGM was dependent on the grinding time. The time required for tablet disintegration of the KGM matrix tablets containing theophylline increased as the grinding time increased; therefore, drug release was sustained. The Higuchi plots of the matrix tablets obtained from KGM ground for 60–120 min exhibited good linearity because they maintained their gel matrix tablet shape during the release test. However, KGM tablets ground for 0–30 min exhibited nonlinear curves, which were caused by tablet disintegration. This suggests that drug release from the KGM matrix tablet can be freely controlled by the degree of mechanochemical treatment.