As a natural mineral, calcium carbonate (CaCO3) is widely investigated for various medical applications. It is a biocompatible material characterized by high degradation rate and great osteoconductivity. Many researchers evaluate CaCO3 in the form of particles as a candidate for use in drug delivery systems. In this study we present an optimization of the process of producing CaCO3 particles by the precipitation method with the use of combinations of different time of ultrasound treatment and surfactant concentrations used. Depending on the synthesis conditions, various sizes of particles were fabricated. The particles were loaded with sodium alendronate (Aln, 5% or 10% by weight) with a relatively high encapsulation efficiency between 40 and 50%, depending on the amount of Aln added and the drug loading of approximately 9% for both cases. MG-63 osteoblast-like cells were contacted with 10% wt./vol extracts of fabricated particles to assess their cytotoxicity. None of the extracts investigated was found to be cytotoxic. Furthermore, an in vitro study in direct contact of MG-63 cells with particles suspended in culture medium was performed. The results showed that the fabricated particles are cytocompatible with osteoblast-like MG-63 cells. However, the higher the concentration of the particle suspension and the greater the amount of alendronate present in the solution, the lower the metabolic activity of the cells was measured. The presented method of CaCO3 particles manufacturing is simple, cost-effective, and allows one to fabricate particles of the required size and shape that are cytocompatible with MG-63 cells in defined concentrations of particle suspensions.