The study aimed to compare the effect of dexmedetomidine added to lidocaine against epinephrine added to lidocaine on local anesthetic potency and to look for future prospects of dexmedetomidine as an additive to local anesthesia in dentistry. The study included 25 healthy volunteers in whom extraction of all first premolars was scheduled as part of their orthodontic treatment plan. In this split-mouth, double-blind, crossover, randomized controlled trial, patients were randomized into 2 groups: Group 1 received injection lidocaine plus dexmedetomidine, and group 2 was administered lidocaine plus epinephrine. Patients were assessed for the onset of action of anesthesia, duration of analgesia, pain perception, and vital signs. The mean values (±standard deviations) for the onset of anesthetic action in groups 1 and 2 were 113±24.9 and 141±34.8seconds, respectively, for the mandible. For the maxilla, the mean values were 113±24.9seconds for group 1 and 165±43.8seconds for group 2. The duration of anesthesia was longer in group 1 (lidocaine plus dexmedetomidine), in which the requirement for the first analgesic on request was seen after a longer time interval, when compared with group 2 (lidocaine plus epinephrine).Pain perception elicited statistically significant results with less perception of pain in group 1 (lidocaine plus dexmedetomidine). The vital parameters remained stable, and the results were not statistically significant. In this study, we observed that the addition of dexmedetomidine to lidocaine for maxillary and mandibular nerve blocks significantly prolonged the block duration and shortened the onset of action, as well as improved postoperative analgesia in terms of the need for fewer analgesics in the postoperative period. Furthermore, the vital parameters remained stable and no complications were encountered. The findings were supportive of the use of dexmedetomidine as an adjunct to local anesthetics in dental procedures.