Rutin, naturally phenolic bioactive compound, is a potent antioxidant and anti-inflammatory activity having poor watersolubility as a weak point. The rapid and simple soluble rutin successfully formed using microwave treatments with stevioside as a natural solubilizer. Soluble rutin was optimized by the Box-Behnken design according to the independent four factors such as stevioside concentration, rutin concentration, microwave power, and microwave treated time, respectively. Finally optimal soluble rutin was obtained around 100% yield at a conditions as 146 mg/mL of stevioside, 5.9 mg/mL of rutin, 50 W of microwave power, and 5 min of treated time. These study illustrated that the soluble rutin formed by stevioside and microwave treatment can be applicable for functional foods and cosmetic materials in pharmaceutical areas.