Biodegradable aliphatic polyesters such as polylactide (PLA) are widely used in medical applications. When employed as an implantable material, the control of the surface properties of PLA is of great interest because biochemical reactions occur on the surface or at interfaces. Thus, chemical modifications of the surface of degradable polyesters can be used to tailor the surface properties while preserving the bulk characteristics. This paper proposes a simple and versatile method of preventing polymer degradation and immobilizing simple molecules, macromolecules, and biomolecules on PLA surfaces. The method is based on a one-pot, two-step procedure: anionic activation under selected conditions followed by propargylation to form a “clickable” PLA surface. This surface is extensively characterized by SEC and fluorescence techniques using a fluorescent probe, confirming both the functionalization and the absence of PLA degradation. An example of the surface immobilization of a bioactive compound is then described: a well-defined α-azido-functionalized poly(quaternary ammonium) synthesized via ATRP is covalently bound to the propargylated PLA surface using “click” chemistry. This covalent grafting is confirmed by SEC and XPS analyses. The increase in surface hydrophilicity is demonstrated by water contact-angle measurements. Finally, a primary investigation is conducted to determine the antibacterial activity of modified PLA surfaces against E. coli and S. aureus.