The design, synthesis, and discovery of dual-target compounds are considered as a promising strategy to develop new drugs with improved safety and efficacy compared with single-target drugs. This necessitates development of the methodologies that enable us to rapidly and accurately achieve the dual-target leads. Applying rosmarinic acid, 18β-glycyrrhetinic acid, rhein, and ferulic acid as template building blocks, we introduced the self-assembling DNA encoded technique to build the library containing 1,000 compounds. These compounds were screened by receptor chromatography with immobilized beta<sub>2</sub>-adrenoceptor (β<sub>2</sub>-AR) and cysteinyl-leukotriene receptor (CysLT), whereby we obtained a derivative of 18β-glycyrrhetinic acid (XC267) that specifically binds to the two receptors. In vitro assessment demonstrated the desired binding affinity of 6.57 × 10<sup>4</sup> M<sup>-1</sup> to β<sub>2</sub>-AR, 2.82 × 10<sup>4</sup> M<sup>-1</sup> to CysLT, and the dissociation rate constant of 7.52 s<sup>-1</sup> to β<sub>2</sub>-AR, 17.2 s<sup>-1</sup> to CysLT. Pharmacological examination with ovalbumin-induced mice demonstrated that XC267 significantly reduced the levels of IL-4, IL-13, and IgE after oral administration of 10 mg/kg. By Western blot analysis, we observed an up-regulated expression of β<sub>2</sub>-AR and a blocked level of CysLT with a dose-dependent manner in pulmonary bronchial. Our results suggest XC627 is a potential candidate to treat asthma by simultaneously regulating the signaling pathway of the two receptors.