Despite the applicable piezoelectric property of BaTiO3 (BT), its biomedical applications have been limited due to its weak bioactivity and osteoconductivity. To overcome these issues, in the present study, (BaxCa1-x)TiO3 (x = 1, 0.9, 0.8, 0.6, and 0) nanopowders were synthesized using a combination of sol-gel and mechanical activation processes. The changes in the chemical, electrical, structural and biological properties of BaTiO3, as a result of the substitution of Bat(2+) with Ca+2 ions, were thoroughly studied. Substitution of Ba2+ with Ca2+ in the host (BaxCa1-x)TiO3 lattice changed the cubic structure of pure BT to tetragonal mode. Moreover, 40 at. % Ca2+ substitution in BT nanopowder ((Ba0.6Ca0.4)TiO3) resulted in decreased crystallite and particle size and reduced dielectric constant. In addition, bioactivity of (BaxCa1-x)TiO3 powder enhanced with increasing calcium content. MTT assay showed that 20 at.% Ca2+ substitution in the BT nanopowder resulted in significant increase in MG63 cell proliferation. Overall, calcium-substituted BT nanopowder could be a suitable candidate for bone repair.