Abstract: Reducing the drug doses and prolonging the postoperative analgesia time are important requirements of clinical local anesthesia. However, All local anesthetic drugs currently used in the clinic and potentially new anesthetic drugs such as biological toxins exhibit limited pharmaceutical effect. Biomaterials such as liposomes and polymeric microspheres can be designed to load local anesthetic drugs to achieve a prolonged duration and on-demand drug release, accordingly satisfying clinical needs. In this review, we briefly summarized the recent developments in the design of drug delivery systems for controlled release of local anesthetic drugs, and introduced the design concept, the function of several representative controlled-release drug systems, and their applications in local anesthesia. We discussed the challenges and future perspectives for biomaterial innovations in this field.