Antibiotic pollution has become a serious concern due to the extensive use of antibiotics, their resistance to removal, and their detrimental effects on aquatic habitats and humans. Hence, developing an efficient antibiotic removal process for aqueous solutions has become vital. Amoxicillin (Amox) is one of the antibiotics that has been efficiently removed from an aqueous solution using hydroxyapatite nanoparticles (HAP NPs). The current study synthesizes and utilizes hydroxyapatite nanoparticles as a cost-effective adsorbent. Adsorbent dose, pH solution, initial Amox concentration, equilibrium time, and temperature are among the factors that have an evident impact on Amox antibiotic adsorption. The (200) mg dose, pH (5), temperature (25) °C, and time (120) min are shown to be the best-optimized values. The nonlinear Langmuir’s isotherm and pseudo-second-order kinetic models with equilibrium capacities of 4.01 mg/g are highly compatible with the experimental adsorption data. The experimental parameters of the thermodynamic analysis show that the Amox antibiotic adsorption onto HAP NPs powder is spontaneous and exothermic.