Parathyroid hormone (PTH) is an 84 amino acid peptide hormone. Produced in the parathyroid glands, it acts primarily on bone and kidney to maintain extracellular calcium levels within normal limits. It has been shown that the first 34-amino acid fragment of PTH is sufficient to bind and activate the PTH type I receptor (PTH1R). The study of reduced-size PTH agonist and antagonist analogues has been the subject of extensive research, for the development of safer and non-parenteral bone anabolic drugs. Recent investigations focusing on the interaction of N-terminal fragments of PTH with PTH1R showed that certain modifications can increase signalling potency in peptides as short as 11 amino acids. To understand the role of single side-chain of all residues of the most active modified PTH(1-11) – H-Aib-Val-Aib-Glu-Ile-Gln-Leu-Nle-His-Gln-Har-NH2 we substituted every L-amino acid with the correspondent D-amino acid, obtaining a library of analogues of PTH(1-11) which tested as agonist. The library was synthesized by SPPS, employing Fmoc protocol. The results of biological tests demonstrated there is a unspecific decrease of activity from D-Val2 to D-Gln10, but they showed that the activity of D-Har11 is the same order of magnitude of the most active modified PTH(1-11) analogue. This behaviour is paralleled by an increase of helix content on going from D-Val2 analogue to D-Har11 analogue according to CD analysis. NMR analysis confirmed that D-Har11 is the most structured peptide. This is in agreement with our previous works where we have demonstrated a correlation between activity and helix content. The importance of a positively charged group in the C-terminal position is shown to be independent of the configuration of last residue.