Abstract: The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are derived from a HBV preS consensus sequence and are N-terminal preferably acylated and optional C-terminal modified. These hydrophobic modified preS-derived peptides of HBV are very effective HBV entry inhibitors as well as HDV entry inhibitors and are, thus, suitable for the inhibition of HBV and/or HDV infection, prevention of primary HBV and/or HDV infection as well as treatment of (chronic) hepatitis B and/or D. The present invention further relates to pharmaceutical and vaccine compositions comprising these hydrophobic modified preS-derived peptides of HBV.