In this study, natural sepiolite samples were treated with hydrochloric and acetic acid solutions at three different concentrations (0.1 M, 0.5 M, and 1.0 M). The effect of acid treatment on the reactivity of natural sepiolite and the change in cement hydration following the addition of natural sepiolite were studied using X-ray diffraction, particle size distribution analysis, inductively coupled spectrometry, thermogravimetric analysis, and isothermal calorimetry. Although acid treatment leads to a slight decrease in the amorphous phase content in natural sepiolite, the reactivity of sepiolite increased. The results indicate that the increase in sepiolite reactivity most likely stemmed from the activation of the Si phase. In addition, acid-treated sepiolite can modify the hydration of cement during the early curing period and hinder the hydration of cement during the later curing period. The compressive strength of specimens with strong acid-treated sepiolite was higher compared with specimens with weak acid-treated sepiolite.