The question regarding forming spherical-like hydroxyapatite nanoparticles in the presence of Euclea natalensis root extracts is complex. However, from the results, it seems that it depends not only on the presence of Euclea natalensis root extracts but also on the contribution of other factors such as drip rate and temperature. The predominant spherical-like shape hydroxyapatite nanoparticles were obtained in the central point of experimental design (drip rate: 1.5 ml/min, amount of Euclea natalensis extracts: 1.20 g, and temperature: 50 o C). No spherical-like shape hydroxyapatite nanoparticles were observed without Euclea natalensis root extracts. Furthermore, the TEM analysis revealed that the spherical shape hydroxyapatite nanoparticles are formed during the nuclei formation and crystal growth step. This suggests that the combination of Euclea natalensis extracts, drip rate, and temperature favours the isotropic particle growth, leading to spherical-like shape hydroxyapatite nanoparticles. Previous work showed that temperature is a driving force in the shape of hydroxyapatite, and the spherical-like shapes were observed at 40 o C . From the present work's experimental evidence, it is impossible to figure out an exact mechanism that governs the spherical-like shape of hydroxyapatite nanoparticles.