Hydroxyapatites of high calcium and phosphate ions adsorption capacity are highly bioactive. However, they cause the removal of these ions from tissue liquids and cell culture media, thus reducing viability and proliferation potential of osteoblasts. Addition of small amount of gypsum (calcium sulfate dihydrate) to such hydroxyapatite-based composites may help to compensate the ions removal and stimulate the osteoblasts growth and proliferation. Therefore, the aim of this work was to enrich the highly porous hydroxyapatite-based composite with gypsum and verify its effect on ions adsorption as well as osteoblasts viability and proliferation. The results showed that addition of 1.5–1.75% gypsum caused short-term calcium ions compensation in media incubated with the composite and time-shifted increase of osteoblasts proliferation. Moreover, presence of gypsum in the composite increased the content of large pores in SBF-incubated biomaterials with no effect on their microstructure or mechanical parameters. Overall, gypsum addition improves the compatibility of hydroxyapatite-based materials with no critical disadvantages for other properties.