Abstract: Polylactic acid (PLA) and its copolymers represent a critical direction in the development of sustainable polymeric materials. In recent years, a novel class of single-molecule multifunctional catalysts has emerged in the field of PLA synthesis. These catalysts utilize supramolecular interactions such as hydrogen bonding and organic coordination to activate lactide and stabilize the growing chain end, thereby exhibiting a synergistic enhancement in both catalytic activity and selectivity. Compared to metal-based catalysts, they offer advantages such as low toxicity and low cost. When compared to multicomponent organic catalysts, they demonstrate superior polymerization controllability and enhanced selectivity. This review summarizes several representative single-molecule bifunctional catalysts, including hydrogen-bonding-based organic bifunctional catalysts, trifunctional organic catalysts, and alkali metal ion-based catalysts that integrate hydrogen-bonding effects and initiation functions within a single molecule, along with their characteristics in catalyzing the ring-opening polymerization of lactide and block copolymerization. The review proposes that future research should focus on developing single-molecule multifunctional catalyst systems that balance high catalytic activity with stereoselectivity, systematically elucidating the structure-activity relationships and unique mechanisms of this class of catalysts from the perspective of supramolecular interactions.