The biocompatibility and osteogenic activity of the newly developed Zr-30Ta and Zr-25Ta-5Ti alloys were systemically evaluated using cell culture experiments. The surface roughness and contact angle of the alloys were assessed using profilometer and drop-shape analyzer. The biological properties of the alloys were evaluated in terms of protein adsorption, cytotoxicity, adhesion, and proliferation of MC3T3-E1 osteoblasts, NIH3T3 fibroblasts, and RAW264.7 macrophages. The osteogenic activity was evaluated by means of the alkaline phosphatase (ALP) activity, extracellular matrix mineralization, and collagen secretion. The immune response was evaluated by determining the macrophage polarization on the samples using flow cytometry. The results indicated that Zr-30Ta and Zr-25Ta-5Ti alloys had better biocompatibility compared with commercially-pure titanium (CP-Ti). The osteogenic activity on the experimental alloys was significantly better than CP-Ti. Zr-30Ta and Zr-25Ta-5Ti alloys also induced a balanced expression of M1 and M2 macrophage phenotypes in the first 24 h. The favorable surface properties and chemical compositions of Zr-30Ta and Zr-25Ta-5Ti alloys were responsible for their improved biocompatibility and osteogenic activity. Overall, it is suggested that Zr-30Ta and Zr-25Ta-5Ti alloys are promising candidates for dental and orthopedic implant applications.