In medical applications, minimizing thermal damage to biological tissue is of utmost importance for cell viability. In this experimental study, the effects of processing parameters on temperature variation during milling of cortical bone were investigated. Using the Taguchi method, optimization of parameters was performed to identify combinations that minimize the thermal rise, thus reducing the risk of necrosis and at the same time preserving bone viability. The effect of cutting tool rotational speed, feed rate, depth of cut and tool geometry on temperature changes in cortical bone samples was analyzed. Bovine femoral cortical bone samples were subjected to controlled milling trials in which temperature changes near the cutting interface were recorded in real time using a camera with a sensitive thermal sensor. Analysis of variance (ANOVA) was used to determine the statistical significance of the effect of parameters on temperature rise. The findings of the study show that there are significant interactions between the machining parameters affecting the thermal response. Statistical analysis showed that the depth of cut was the most important factor on cortical bone processing temperature, contributing 52.1% in reducing temperature values. It is followed by the number of cutting tool teeth with 23.77% and rotational speed with 18.59%. The optimal machining conditions that minimize thermal damage identified by the study provide effective baseline information for safer and more efficient bone milling procedures.