Pouzolzia zeylanica L. Benn is a perennial herb. It owns many bioactive compounds which is known to possess antioxidant, antimicrobal and anticarsinogenic properties. The purpose of this study was to optimize the operation condition of spray drying of aqueous extract from air dried Pouzolzia zeylanica plant. Maltodextrin and arabic gum were used as carrier in the spray drying process. The Response Surface Methodology (RSM) with 3-level factorial design was applied for process optimization and investigation of the influence of the inlet hot air temperature (170 to 190^oC) and feed flow speed (16 to 20 rpm) on moisture content, particle size distribution and bioactive compounds (polyphenol, flavonoid and tannin content). The particle size was determined using scanning electron microscope (SEM); the content of bioactive compound was determined using spectrophotometer (with Folin-Ciocalteau and Folin-Denis reagent for polyphenol and tannin; aluminium chloride method for flavonoid). The optimum process parameters to produce spray dried powder with the highest bioactive compounds content, the lowest moisture content and the smallest particle size were obtained at the inlet spray drying temperature of 179.92^oC and feed flow speed of 18.12 rpm. At these optimal conditions, the properties of the obtained spray dried in particle size; 6.51 in moisture content and polyphenol, flavonoid, and powder were 6.12 mm, tannin content were 27.80 mg GAE/g, 31.69 mg QE/g and 25.41 mg TAE/g, respectively. The obtained experimental results adequately fit to empirical quadratic models and agreed with predicted within a 95% confidence interval. The process was successfully in laboratory equipment and the product can be used as instant tea for health strengthening.