The γc-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 γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Peptide and/or peptide derivative antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity are described. Also described are peptide and/or peptide derivative antagonists exhibiting Simul-Block activity, and inhibiting the activity of multiple γc-cytokine family members.