Abstract: Reducing the drug administration times and prolonging the postoperative analgesia duration are important requirements of clinical local anesthesia. However, both local anesthetics currently used in the clinic and potentially new anesthetic drugs such as biological toxins have limited pharmaceutical effect. Biomaterials such as liposomes and polymeric microspheres can be designed to load local anesthetics 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 anesthetics, and introduced the design principle, the function of several representative drug controlled release systems, and their applications in local anesthesia. We also discussed the challenges and future perspectives in this field.