The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a negative regulator of hepatic LDL receptors (LDLR) and clinical studies with PCSK9 inhibiting antibodies demonstrated strong LDL-c lowering effects. Here we screened phage-displayed peptide libraries and identified the 13-amino acid linear peptide Pep2-8, which is the hitherto smallest PCSK9 inhibitor with a clearly defined mechanism of inhibition. Pep2-8 bound to PCSK9 with a KD of 0.7 µM, but did not bind to other proprotein convertases. It fully restored LDLR surface levels and LDL particle uptake in PCSK9-treated HepG2 cells. The crystal structure of Pep2-8 bound to C-terminally truncated PCSK9 at 1.85Å resolution showed the peptide to adopt a strand-turn-helix conformation, which is remarkably similar to its solution structure determined by NMR. Consistent with the functional binding site identified by an Ala scan of PCSK9, the structural Pep2-8 contact region of about 400 Å2 la rgely overlapped with that contacted by the EGF(A) domain of the LDLR, suggesting a competitive inhibition mechanism. In agreement, Pep2-8 inhibited LDLR and EGF(A) domain binding to PCSK9 with IC50 values of 0.8 µM and 0.4 µM, respectively. Intriguingly, Pep2-8 mimicked secondary structural elements of the LDLR-EGF(A) domain that interact with PCSK9, notably the β-strand and a discontinuous short α-helix, and it engaged in the same β-sheet H-bonds as EGF(A) does. Even though Pep2-8 may not be amenable to therapeutic applications, the study demonstrate the feasibility of developing peptidic inhibitors to functionally relevant sites on PCSK9.