Abstract: Disclosed are a combination of active components inducing synergistic effects of multi-targeting and a use thereof. More particularly, disclosed are a functional food composition, a cosmetic composition, a pain-suppressive composition, and a composition for treatment or prevention of pruritus or atopic dermatitis, which comprise as active components, two or more components selected from a group consisting of (a) a 5-hydroxytryptamine subtype 2 (5-HT2) receptor antagonist; (b) a P2X receptor antagonist; and (c) any one of a glycine receptor agonist, a glycine transporter (GlyT) antagonist, a gamma-aminobutyric acid (GABA) receptor agonist, and a GABA transporter 1 (GAT1) antagonist. The multi-targeting composite composition (specifically, natural substances composite composition) has synergistic effects, and thus a treatment using a combination of respective components may achieve increased biological effects, in which mechanisms targeted by respective components are involved.