Cocktail therapy by delivering multiple drugs to diseased cells can elicit synergistic therapeutic effects and better modulate the complex cell-signaling network. Besides selection of drug combinations, a difficulty in delivery is how to encapsulate drugs with various solubility into a common vehicle, particularly when both hydrophobic and hydrophilic compounds are involved. Furthermore, it is highly desirable that the drug release profile can be controlled in an on-demand fashion for balanced therapeutic and side effects. On the basis of a simple and scalable double emulsion approach, we report a new class of nanocapsules that can solve these problems simultaneously. Further linking the nanocapsules with peptides targeting cell surface integrins leads to significantly enhanced cell uptake of the nanocapsules. Intracellular drug release triggered by external stimuli has also been achieved without affecting cell viability. Further development of this technology should open exciting opportunities in treating tough diseases such as cancer, cardiovascular diseases, neurological disorders, and infectious diseases.