A directing-group-free strategy for oxidative regioselective aminochalcogenation of indolines with amines and dichalconides is presented. This strategy combines tandem coupling sequences and oxidative dehydrogenation methods in a multi-component reaction, enabling the fast construction of a series of C2,3- or C2,5-aminochalcogenated indole derivatives. Moreover, the application of this synthetic approach is demonstrated through the late-stage modification of pharmaceuticals and the derivatization of the products, highlighting its potential and significance.