In recent years peptide YY (PYY) has attracted attention within the area of diabetes and obesity due to its involvement in food intake regulation and glucose homeostasis. It is well-known that PYY1-36 is rapidly cleaved by dipeptidyl peptidase-4 to the more Y2 receptor selective analogue PYY3-36, which is further cleaved to the inactive analogue PYY3-34. In order to improve the selectivity and proteolytic stability of the C-terminus, we synthesized several analogues incorporating N-methyl amino acids or β-homo amino acids and other non-natural amino acids. These were tested against all four NPY receptors, and highly potent and Y2 receptor selective analogues were identified by combining a tryptophan residue in position 30 with either N-methyl or β-homo arginine in position 35. We also identified an analogue with a MeGln34 substitution that surprisingly displayed high affinity toward all four receptors. In addition, these analogues displayed improved stability toward C-terminal proteolysis compared to native PYY3-36.