Abstract: The ?c-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of ?c-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. The present embodiments relate to the design of peptide antagonists based on the consensus ?c-subunit binding site to inhibit ?c-cytokine activity. In several embodiments, peptide antagonists exhibit Simul-Block activity, inhibiting the activity of multiple ?c-cytokine family members.