Poly([R]-3-hydroxy-10-undecenoate) (PHUE) is a biodegradable/biocompatible polyester from polyhydroxyalkanoates (PHAs) family, used in biomedical applications. PHA's introduction to the body may have implications on cell membrane stability—this motivates studies of interactions between PHAs and phospholipids, main membrane constituents. Interaction analysis in PHUE monolayers with two phospholipids (different hydrophilic groups), phosphatidylserine (DOPS), and phosphatidylethanolamine (DOPE), shows that repulsive interactions between PHUE and DOPS and attractive between PHUE and DOPE resulted from different lipid headgroup size and orientation at the air–water interface (PE, parallel to the interface, attracted PHUE via hydrogen bonds, ion–dipole, and dipole–dipole interactions).