Polylactide (PLA), as one of the most extensively studied synthetic aliphatic polyester, offers the prospective applications in a number of fields, such as implant materials, degradable sutures, drug carriers, and tissue engineering scaffolds. However, some of its properties, such as its hydrophobic and semicrystalline properties and absence of functional or reactive groups along the polymer backbone, limit its medical applications. In this chapter, PLA functionalization method was summarized and the application of the functionalized PLAs in drug delivery, artificial oxygen carriers, and protein separation and purification was concisely reviewed.