In this study, we evaluated the effects of two types of hydroxyapatite (HAP) nanoparticles, sharing the same surface chemistry but differing in shape, on the biological characteristics of plasma, platelets and red blood cells. Initially, two different shapes (rod-shaped and sphere-shaped) of HAPs were characterized. These HAPs were then co-cultured with plasma and red blood cells to examine their impact on coagulation and hemolysis. The impact of HAPs on white blood cells count in mice were evaluated following gavage and tail vein injection. Sphere-shaped HAP is more likely to adsorb onto platelet surfaces, while rod-shaped HAP is more likely to cause hemolysis. Although there are differences in the experimental results between sphere-shaped HAP and rod-shaped HAP, both types demonstrate good blood compatibility at a 20 mM concentration. Furthermore, experiments showed that sphere-shaped nano-HAP induced a more pronounced increase in white blood cell count, suggesting that it may exhibit greater toxicity. While differences exist in the blood compatibility test results between the two HAPs, these differences are minimal, with both results falling within a safe range. Overall, HAP demonstrates excellent blood compatibility.