An efficient multicomponent protocol has been developed to access two different kinds of peptide–ecdysteroid conjugates. The approach exploits the reactivity of the 6-keto-7-ene group of 20-OH-ecdysone, allowing the unprecedented preparation of 6-amino and 6-isocyanide derivatives. The ecdysteroid derivatives were further employed in the Ugi reaction, together with formaldehyde and various structurally diverse carboxylic acids, isocyanides and amines, to afford a small family of potential multidrug-resistance modulators.