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Compartmentalization protected biomolecules from the fluctuating environments of early Earth. Although contemporary cells mostly use phospholipid‐based bilayer membranes, the utility of non‐bilayer compartments was not ruled out during the prebiotic and modern eras. In the present study, we demonstrated the prebiotic synthesis of lipidated cationic amino acid‐based amphiphiles [lauryl ester of lysine (LysL); ornithine (OrnL); and 2,4‐diamino butyric acid (DabL)] using model dry‐down reaction. These amphiphiles self‐assemble into micellar membranes. However, the OrnL and DabL‐based micelles undergo pH‐responsive transformation to lipid droplet‐like morphologies, a modelcompartment in the prebiotic Earth. These cationic droplets encapsulated prebiotic molecules (isoprene) and assisted electron transfer reaction to synthesize isoprenoid derivatives at primitive Earth conditions. The self‐assembly of prebiotic amphiphiles, their transformation to droplet compartments, and droplet‐assisted C−C bond formation reaction might have helped the evolution to synthesize various biomolecules required for the origin of life. [ABSTRACT FROM AUTHOR]