Clarithromycin (CAM) is known to be poorly water-soluble and acid-labile drug. Various alkalizers such as MgO, Na2CO3, Na2HPO4 and NaHCO3 were utilized to modulate the microenvironmental pH (pHM) and to improve the low stability and solubility of CAM in a crystalline-solid dispersion system (CSD). Polyvinylpyrrolidone (PVP K-30) and hydroxypropylmethylcellulose (HPMC) 4000-based CSDs containing alkalizers were prepared by cosolvent precipitation followed by evaporation process. The dried-CSDs mixed with microcrystalline cellulose, 2% croscarmellose sodium, and 1% magnesium stearate was then directly compressed into tablet. A dissolution test was carried out in 900 mL of pH 5.0 buffer solutions at 37 °C with a 50 rpm paddle speed. pHM, surface morphology, and structural behaviors were investigated. The dissolution rates of CAM in CSD containing alkalizers were improved. The drug in CSD remained crystalline as observed by differential scanning calorimetry and powder X-ray diffraction. Scanning electron microscopy revealed nearly identical images regardless of the sorts and amounts of carriers. PVP-based CSD tablet without alkalizer showed greater drug release, while HPMC-based CSD tablet without alkalizer retarded drug release due to its greater swelling capability. However, when the alkalizers were added in CSD tablet, the drug release was sharply increased. NaHCO3 induced the most rapid drug release while MgO retarded drug dissolution. Alkalizers in CSD also could maintain the pHM of the tablet above pH 5 under acidic conditions. The use of pH modifiers in CSDs could provide a useful method to improve the dissolution rate and stability of CAM via modulation of pHM without changing drug crystallinity.