Abstract: Calcium is one of the most important metal elements related to life activities and biochemical processes. It plays an important role in biochemistry and medicinal chemistry. However, due to its saturated electronic structure as one of the alkaline earth metals and its characteristics of hard acids, Ca²⁺ shows weak coordination properties, there are relatively few studies on its complexes, and even fewer on calcium(II) complexes related to pharmacological activities and the corresponding applications. In this review, we focused on the significant biological activity and potential pharmacological activities of Ca²⁺, and summarized the research progresses in recent years with regard to the syntheses and the related biological activity studies of the Ca(II) complexes of bio-active ligands. Besides, the preliminary research achievements targeting the new veterinary Ca(II) complexes of fluoroquinolones are introduced on the basis of our recent research work, so as to provide reference for further exploration and understanding of the pharmacological activities and physiological functions of the Ca(II) complexes.