A mild, greener approach via tandem-Michael-cyclization cascade reaction towards the construction of a group of di- and tri-differently substituted indolizine with a broad scope of the substrate is described. The synthetic route to indolizine having different substituents, benzoyl at C5, alkyl/aryl, at C6, and ester at C7 positions is established where different N-alkylated pyrrole-2-carbaldehydes and electron-deficient acetylenes are employed for the synthesis of pyridine moiety. This methodology features water-mediated reactions compatible with various functional groups affording indolizines in good yield without using any oxidant, additive, or catalyst as well. Successfully this methodology has been extended to prepare dicarboxylate and nitrile-substituted indolizines which can be proven important from a biological activity point of view in future.