This study was designated for preparation of cockle shell nanoparticles and evaluation of drug release from alginate/cockle shell nano bio composite bone scaffold. Materials & Methods: In this study, nano cockle shell powder was prepared by mechano-chemical method utilizing ball milling machine and tween 80. The prepared nano cockle shell powder was characterized by scanning electron microscope (SEM) and transmission electron microscope (TEM) to investigate the morphology and size of the prepared nano cockle shell particles. After that, sodium alginate (SA)/cockle shell scaffold was fabricated by freeze-drying technique and then loaded with 1% and 2% chlorhexidine by a stirring process. The fabricated scaffold was characterized by SEM, TEM, FTIR and EDX. Finally, drug encapsulation and drug release were evaluated by using UV-spectrophotometer. Results: The scanning electron microscope (SEM) results showed that the prepared cockle shell powder was present in the form of nano particles with particle size range from(63nm-145nm). Moreover, it revealed that the prepared scaffold had a porous structure and a homogenous distribution of calcium ions that crosslinked to alginate polymer chains. The FTIR spectra of the prepared alginate/calcium carbonate scaffold showed that CHX drug was successfully loaded into alginate/cockleshell scaffold. As regard to the drug release, the 2% loaded scaffold recorded higher significant percentage of drug release than the 1% CHX loaded scaffold at different time intervals. Conclusion: Based on the overall results, the CHX loaded alginate/ nano calcium carbonate scaffold has proved to be a suitable nanocarrier that exhibits a sustained release of CHX drug for many hours. Thus, it could be considered as an effective bone scaffold in treatment of infectious bone diseases