Heat treatment of sorghum kernels has the potential to improve their nutritional properties. The goal of this study was to assess the impact of dry heat treatment at two temperatures (121 and 140 °C) and grain fractionation, on the chemical and functional properties of red sorghum flour with three different particle sizes (small, medium, and large), for process optimization. The results showed that the treatment temperature had a positive effect on the water absorption capacity, as well as the fat, ash, moisture and carbohydrate content, whereas the opposite tendency was obtained for oil absorption capacity, swelling power, emulsion activity and protein and fiber content. Sorghum flour particle size had a positive impact on water absorption capacity, emulsion activity and protein, carbohydrate and fiber content, while oil absorption capacity, swelling power and fat, ash and moisture content were adversely affected. The optimization process showed that at the treatment temperature at 133 °C, an increase in fat, ash, fiber and carbohydrate content was experienced in the optimal fraction dimension of red sorghum grains. Moreover, the antioxidant performance showed that this fraction produced the best reducing capability when water was used as an extraction solvent. Starch digestibility revealed a 22.81% rise in resistant starch, while the thermal properties showed that gelatinization enthalpy was 1.90 times higher compared to the control sample. These findings may be helpful for researchers and the food industry in developing various functional foods or gluten-free bakery products.