The nature of the surface is critical in determining the biological activity of silica powders. A novel correlation between toxicity and surface properties of bioactive glass ceramics (BGCs) synthesized via the sol-gel method was attempted in this study. The behavior of BGCs after their attachment to the surface of red blood cells (RBCs) was evaluated and their toxic effects were determined based on hemolysis, membrane injury via anti-phosphotyrosine immunoblot of Band 3, lipid peroxidation, potential to generate reactive oxygen species, and antioxidant enzyme production. In particular, three BGCs were synthesized at three calcination temperatures (T1=835 °C, T2=1000 °C and T3=1100 °C). Their toxicity based on hemolysis was dose dependent, while BGC-T2 had the best hemocompatibility in compare with the other BGCs. No BGCs in dosages lower than 0.125mg/ml could damage erythrocytes. On the other hand, all BGCs promoted the production of reactive oxygen species in certain concentrations, with the BGC-T2 producing the lowest ROS and increasing the glutathione levels in RBCs protecting their damage. The results suggest that various factors such as size, a probable different proportion of surface silanols, a balanced mechanism between calcium and magnesium cellular uptake or the different crystalline nature may have contributed to this finding; however, future research is needed to clarify the underlying mechanisms.