Design of Experiments (DOE) is a necessary component of product development and improvement, and prepares a scientific approach to evaluation and optimization of experimental factors. This study presents the application of DOE to homemade yogurt production process in order to detect the critical process factors which influence pH values of homemade yogurt and identify the optimal setting for these effective factors. Homemade yogurt were made by changing two different levels of skim milk powder, inoculation temperature, incubation temperature, incubation time, and fat to investigate main and interactions effects on pH of the fermented milk and achieve the optimal pH value from customer prospective in the range of 4.2 to 4.6. The results demonstrated that incubation time and fat are the most effective factors on pH development and the optimal settings for these factors should be 43200 seconds (12 hours) for the incubation time and 17.83 (g/kg) for the fat.