Background: Postoperative analgesia (POA) is an important determinant of successful treatment. Dexmedetomidine (DEX) has recently gained attention as a promising adjuvant to local anesthetics (LA). The present study aimed to evaluate the efficacy and safety of levobupivacaine (LB) as an adjuvant during inferior alveolar nerve block (IANB) in the extraction of lower impacted third molars (LITM). Methods: A prospective, randomized, placebo-controlled, triple-blind, parallel-arm, and clinical study was performed on 50 systemically healthy participants who required removal of an asymptomatic LITM. Using a 1:1 distribution, the participants were randomized into two groups (n = 25). Group L (control group) received 1.8 mL of 0.5% LB and 0.2 mL normal saline (placebo) and Group D (study group) received a blend of 1.8 mL of 0.5% LB and 0.2 mL (20 µg) DEX. The primary outcome variable was the duration of POA and hemodynamic stability, and the secondary variable was the total number of analgesics required postoperatively for up to 72 h. The participants were requested to record the time of rescue analgesic use and the total number of rescue analgesics taken. The area under the curve was plotted for the total number of analgesics administered. The pain was evaluated using the visual analog scale. Data analysis was performed using paired students and unpaired t-test, Mann–Whitney U test, Chi-square test, and receiver operating characteristic analysis. Statistical significance was set at P < 0.05. Results: The latency, profoundness of anesthesia, and duration of POA were statistically significant (P < 0.05).The differences between mean pain scores at 6, 12, 24, 48, and 72 h were found to be significant (each P = 0.0001). Fewer analgesics were required by participants in group D (2.12 ± 0.33) than in L (4.04 ± 0.67), with a significant difference (P = 0.0001). Conclusion Perineurally administered LA with DEX is a safe, effective, and therapeutic approach for improving latency, providing profound POA, and reducing the need for postoperative analgesia.