Objective This article aims to fabricate, characterize, and evaluate the mechanical strength and cytotoxicity of biphasic hydroxyapatite/calcium sulfate (HA/CS) blocks using partial hydrothermal conversion of gypsum blocks. Materials and Methods Gypsum blocks were immersed in Na3PO4 solution under hydrothermal conditions at 150 °C for 6, 12, and 24 hours, denoted as 6-HA/CS, 12-HA/CS, and 24-HA/CS, respectively. After that, the phase composition was analyzed using X-ray diffraction. Diametral tensile strength (DTS), solubility in Tris-HCl buffer, and cytotoxicity on cell cultures were measured. Results Hydrothermal treatment produced biphasic HA/CS with increasing hydroxyapatite content. All HA/CS groups exhibited a significant reduction in DTS (~0.5–0.7 MPa) compared with gypsum (2.06 MPa; p < 0.05). Solubility was lower in HA/CS than in gypsum (206.15 mg/L), with the 24-HA/CS group showing the lowest value (94.70 mg/L). Cytotoxicity testing demonstrated cell viability above 70% for all groups, meeting ISO standards of non-cytotoxicity. Conclusion Partial hydrothermal conversion of gypsum block successfully produced biphasic HA/CS with tunable phase composition, reduced solubility, and acceptable cytotoxicity. © 2026. The Author(s).