Here, we introduce the synthesis, characterization, and surface orientation properties of a new generation of biodegradable and biomimetic polymers. These phospholipid-mimetic, biodegradable polymers are synthesized by combining poly epsilon-caprolactone (PCL) with various functional polar end-groups, including zwitterionic phosphoryl choline (PC), anionic succinic acid, and cationic quaternary ammonium. The polyester backbone provides mechanical stability and biodegradability, whereas the various headgroups provide a variety of functions. The careful evaluation of the synthesis has allowed reaction conditions to be optimized, leading to complete conversion at each step and, subsequently, high yields of PCL-PC. Analysis of the ability for trimethylamine to cause any adverse transesterification reactions has shown that no molecular scrambling occurs either with two low-molecular-weight esters or with PCL. Therefore, the PCL initially present is retained throughout the synthesis. In parallel to the polymer synthesis, a model synthesis was conducted using benzyl 6-hydroxy hexanoate as a starting point, to aid the conversion studies and spectroscopic characterization. We ascertained from this feature that such synthesis allows the formation of any molecular architecture with targeted functionalities. The film properties of the PCL-PC amphiphile product revealed surface enrichment behavior, because the polar PC headgroup is oriented toward the surface. This followed the treatment of a cast film in a hydrophilic environment, as observed by electron spectroscopy for chemical analysis.