Microalgae Spirulina (Arthospira platensis) contains high protein content (55-70%), consisting of approximately 20% phycocyanin compounds as a photosynthetic pigment. Phycocyanin has antioxidant and anti-inflammatory properties. This study aims to obtain the optimum condition for extracting phycocyanin from Spirulina (Arthospira platensis) in ultrasound-assisted extraction using three different solvents. A Response Surface Method (RSM) optimization technique is used to obtain the significance of the multivariable effect on the extraction process. Based on the result, it was determined that the sodium buffer phosphate was the most suitable solvent for extraction phycocyanin compared to acetic acid and ethanol. Acetic acid solvent and ethanol solvent failed to provide high yield and purity of phycocyanin as the chlorophyl and its derivative also present on the extract (co-extracted). The optimum conditions of UAE with sodium buffer phosphate were at stirring speed of 1000 rpm, temperature of 40 oC, and solvent to biomass ratio of 100:1. The results presented that temperature had significant influences on the yield of phycocyanin. The high coefficient of determination (R2) value obtained in this study (0.9153), which indicate that the model was not only accurate but also adequate and reliable in predicting optimal conditions.