Instant controlled pressure drop (DIC) technology was utilized in the production of glucose from sago pith waste (SPW). In situ autohydrolysis was conducted in a DIC reactor to obtain the maximum glucose production. The influence of pressure, acid concentration, and treatment time on the glucose yield from SPW subjected to DIC-assisted in situ autohydrolysis was determined, and the experimental conditions were optimized using the response surface method. The results showed that the linear term of acid concentration and the quadratic terms of pressure and time had a significant effect on the glucose yield. The optimized experimental conditions for maximum glucose production (48.21%) from SPW subjected to DIC-assisted autohydrolysis were a pressure of 0.1 MPa, acid concentration of 0.1 M, and time of 4 min. The findings demonstrated that DIC technology has the potential to be utilized for the commercial production of glucose from SPW.