The rind of melon seeds (Cucumis sativus L.) contains a flavonoids, alkaloids, saponins, and anthraquinone which has an antibacterial activity for acne. Nanoemulsion are known to increase the penetration of substances on the skin because they are influenced by the addition of surfactants and cosurfactants. So it is necessary to make nanoemulsion by combining Tween 20 and Sorbitol. This study aims to determine the effect of the combination of Tween 20 and Sorbitol on the pH, viscosity, % transmittance, and determine the good stability of the optimum formula. Methods: Melon seeds was extracted by the maceration method using 96% ethanol as solvent. The manufacture of nanoemulsion using the spontaneous emulsification method and designed in the Design Expert 13.0.0 program using the Simplex Lattice Design (SLD) method. Results: Based on the results of the study showed that the composition optimum of Tween 20 obtained 30% and Sorbitol obtained 20% generate predictive value PH 4,82%, Viscosity 167,917, and %transmittance 97,595%, desirability value 0,760 and particle size 98,7-107,2 nm. Conclusion: The preparation of red watermelon rind extract nanoemulsion with a combination of Tween 20 and Sorbitol give a significant effect on pH, viscosity, % transmittance and stability did not give significant changes in organoleptic, viscosity, pH, and nanoemulsion type tests.