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. Thus, the multi-targeting composite composition may not only remarkably control pain but may also increase effects of: alleviating symptoms of skin diseases such as itching and atopic dermatitis； preventing or improving depression, refreshment, pore minimization, improving wrinkles, skin regeneration, skin health, recovery of skin condition, skin whitening, preventing or improving athlete's foot, recovery of scalp health and regeneration of scalp, promoting hair growth, preventing gray hair, and improving dental and periodontal diseases, etc.
