Jerusalem artichoke is an important natural matrix for inulin production. In this experiment, response surface methodology (RSM) was employed to optimize the spray-drying parameters in order to determine the maximal inulin yield. For this study, three independent variables (heating temperature (Tª, 110–120 °C), creep speed (V, 18–22 rpm) and pressure (P, 0.02–0.04 MPa)) were used in the experimental design. Using the Box–Behnken design, the optimal parameters obtained were: drying temperature 114.6 °C, creep speed 20.02 rpm, and pressure: 0.03 MPa. The inulin yield, water content and particle size of inulin obtained by spray-drying and freeze-drying were compared. In this regard, the spray-dried inulin consisted of a white powder having a fine particle size, and the freeze-dried inulin had a pale-yellow fluffy floc. On the other hand, the drying methods had a great influence on the appearance and internal structure of inulin powder, since the spray-dried inulin had a complete and uniform shape and size, whereas the freeze-dried inulin had a flocculated sheet structure. The analysis showed that the spray-drying led to a higher inulin yield, lower water content and better surface structure than freeze-drying.