In this study highlights on the optimization of extraction process parameters of total phenolic content and antioxidant activity from Spirulina platensis, through ultrasonication (probe) technology. Especially, optimization of ultrasonication parameters was carried out employing Box-Behnken Design (BBD) and response surface methodology. Alongside the three levels of extraction parameters i.e. solvent volume, extraction time and frequency have been fixed. As responses, the total yield of extract, total phenolic content and DPPH radical scavenging activity (IC50) of the extracts were determined. The variability of each response variable was determined by developing multiple linear regressions. The statistical analysis (ANOVA) of developed mathematical models allowed the prediction of the behaviour of the responses, as a function of the variables involved in the process. The optimized extraction conditions were obtained at 58.76 kHz frequency, 10 mL of solvent volume for 6 min. Simultaneously this extract exhibited the highest content of total phenolic content (30.89 mg GAE/g powder), IC50 for DPPH activity (151.27 µg/mL). The extract exhibited an important antioxidant i.e. caffeic acid, which was quantified as 660.72±41.05 µg/g of dry algal powder using HPLC. In spite of fact that, this study offers an alternative method for obtaining natural antioxidants from algae for food and pharmaceutical applications. Keywords: Microalgae; Probe sonication extraction; Total phenolic content; Antioxidant activity