The effects of cryoprotectants on the diameter and the entrapment efficiency of ibuprofen-loaded solid lipid microparticles (SLM) during the freeze-drying process were investigated extensively. The SLM were prepared by the emulsion–congealing technique in which a glycerol behenate was used as the lipid matrix for the SLM and a soybean lecithin/bile salt used as the stabilizer. Also, trehalose, glucose, mannitol, and sucrose were chosen as the cryoprotectants. Trehalose and glucose proved to be the most effective in preventing particles aggregation and in inhibiting leakage from drug-loaded particles during the SLM freeze-drying process. The most suitable concentrations were proved to be 15% and 5% (wt), respectively.