Asymmetric N-alkylations of isatins with enals were shown to be feasible via a prolinol-catalyzed iminium activation, and N-alkylated isatins were obtained in good yields and with excellent enantioselectivity. The biologically useful N-alkylated isatins also served as valuable synthetic precursors, and could be readily converted to chiral N-alkylated indole derivatives. The described method provides a novel entry to access optically enriched N-alkylated isatins and indole derivatives.