Cockle shells are a natural reservoir of calcium carbonate (CaCO3), which is widely used in bone repair, tissue scaffolds, and the development of advanced drug delivery systems. Although many studies report on the preparation of CaCO3, the development of a nanosized spherical CaCO3 precursor for calcium oxide (CaO) that is suitable to be incorporated in dental material was scarce. Therefore, this study aimed to synthesize a nanosized spherical CaCO3 precursor for CaO derived from cockle shells using a sol–gel method. Cockle shells were crushed to powder form and mixed with hydrochloric acid, forming calcium chloride (CaCl2). Potassium carbonate (K2CO3) was then fed to the diluted CaCl2 to obtain CaCO3. The effect of experimental parameters on the morphology of CaCO3, such as volume of water, type of solvents, feeding rate of K2CO3, and drying method, were investigated using field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffractometry (XRD), Brunauer–Emmett–Teller surface area analysis, and thermogravimetric analysis. Optimized CaCO3 was then calcined to form CaO. XRD analysis of CaCO3 nanoparticles was indicative of the formation of a calcite phase. The well-structured spherical shape of CaCO3 was obtained by the optimum condition of the addition of 50 mL of water into CaCl2 in ethanolic solution with a 1 h feeding rate of K2CO3. Less agglomeration of CaCO3 was obtained using a freeze-drying technique with the surface area of 26 m2/g and average particle size of 39 nm. Spherical shaped nanosized CaO (22–70 nm) was also synthesized. The reproducibility, low cost, and simplicity of the method suggest its potential applications in the large-scale synthesis of the nanoparticles, with spherical morphology in an industrial setting.