Bone materials are mainly composed of an inorganic constituent called hydroxyapatite (HA). In the current study, mesoporous Zn2+/Ag+ doped hydroxyapatite nanoparticles (Zn-Ag doped HA) with high antibacterial activity were synthesized through ultrasonic coupled sol-gel techniques under calcination temperatures of 600 °C for 4 h and 1100 °C for 1 h. The variance in the molar ratio of Zn2+/Ag+ in Ca9.0Zn1.0−xAgx(PO4)6(OH)2 (x = 0.0, 0.25 to 1.0) and its effects on the chemical and physical properties of the powdered samples were investigated. The results show that the hexagonal framework of HA incorporated both the Zn2+ and Ag+ ions and the rhombohedral structure of β-TCP. The main functional groups of HA and Zn-Ag doped HA samples were hydroxyl and phosphate. All samples have mesoporous characteristics with a Type IV isotherm. The agar well diffusion process was used to examine antibacterial activity against E. coli, P. aeruginosa, S. aureus, B. cereus and B. subtilis. Effective antibacterial activity was displayed by Zn-Ag doped HA. Excellent antibacterial performance was shown by Ca9.0Zn0.75Ag0.25(PO4)6(OH)2 against all tested bacterial strains, except P. aeruginosa. This material showed inhibition zones ranging from 7 to 11 mm, implying that it is a suitable material with an antibacterial action for environmental applications, specifically for water purification.