WDR5 is an adaptor protein involved in the regulation of various epigenetic modifier complexes. Various inhibitors have been described but only as inhibitors of its protein-protein interactions. Here we describe peptidic macrocycles that act as inhibitors of the interaction between WDR5 and long non-coding RNAs. The findings provide a new strategy to modulate the biological function of WDR5 as an RNA binding epigenetic regulator.