A sustainable, economical, and straightforward synthetic route based on the higher-order multicomponent reactions (MCRs) approach for the unification of biologically significant quinoxaline-pseudopeptide-triazole pharmacophores in a sole structure, is developed. The planned strategy comprises a one-pot, six-component, tandem cyclocondensation/Ugi/click reaction sequence, which leads to highly complex pharmaceutically desirable compounds from easily accessible precursors. The salient features of the present procedure are benign reaction conditions, energy efficiency, operational simplicity, pot economy (construction of three pharmacophores in a one-pot reaction), high bond-forming economy (formation of eight new bonds), high atom economy (water as the only by-product), and excellent overall yields. © 2023 The Royal Society of Chemistry.