Midgut extracts play crucial roles in food digestion and detoxification. We evaluated the effect of pH on the profiles of the midgut extracts in rice leaffolder, Cnaphalocrocis medinalis and the degradation of activated Bt-toxins by the midgut extracts under different pH conditions. Total protease activity increased slightly with the increase with the simulated pH in the midgut extracts and the maximal protease activity was observed at pH 10.5, while an upward trend was observed as the pH of reaction buffer increased. Activity of chymotrypsin-like enzymes increased with pH, both in the buffer and midgut extracts, while the activity of trypsin-like enzyme was unaffected. Degradation of the activated Cry2A by the midgut extracts enhanced as the pH increased. Cry2A was fully degraded into smaller segments at pH 9.0–10.5. Activated Cry1C protein at pH 9.0–10.5 was partially degraded by the midgut extracts. Activated Cry1Aa and Cry1Ac were partially degraded into fragments by the midgut extracts at high pH. These results will facilitate our further understanding of the interactions between C. medinalis and the Cry toxin.