Abstract: Due to their lack of a specific structure and dynamical nature, targeting of epitopes that are part of an intrinsically disordered region of a protein is a notoriously difficult task. Here, we describe a computational approach to overcome this problem, based on the use of a protein folding algorithm within a Monte Carlo optimization pipeline to generate peptide binders that bind by co-folding with their epitope. For different protein targets, we show by accurate free-energy calculations that our approach is able to design strong binders, with binding free energies of the order of tens of $k_B T$ (i.e. stronger than 50 kJ/mol), corresponding to $K_D$ values in the nM regime or lower. Direct observation of the molecular structures during the binding process shows the binder and targeted epitope fold upon binding and acquire a structure not presented in their unbound state, suggesting that co-folding is the implied mechanism, and that the latter is correctly described by the protein folding algorithm we employ. Given the ubiquitous presence of unstructured regions in proteins, our results suggest a potential pathway to design drugs targeting a large variety of previously untargetable epitopes and opens new possibilities for therapeutic intervention in diseases where disordered proteins play a key role.