There is a growing pressure for the development of sustainable and environmentalfriendly source of energy such as ethanol that could substitute the depleting fossil fuels. Papaya waste including papaya seed and papaya peel is one of the main fruit wastes in Southeast Asia which has great potential to be utilized as substrate for bioethanol production. In this study, papaya waste was fermented to produce bioethanol using Saccharomyces Cerevisiae. The effect of pH, temperature, and incubation time on bioethanol production was studied within the range of 3.0- 6.0, 25-45°C and 24-96 h, respectively. These parameters were optimized using Response Surface Methodology (RSM) based Box-Behnken Design (BBD). It was found that a maximum ethanol concentration of 0.2224 g/ml was obtained from papaya waste at pH 4.5, 45°C and 24 hours. The significance of the parameters increased from incubation time, pH to temperature. © 2023, Association of American Publishers. All rights reserved.