This study investigates the clinical effectiveness and safety of combining articaine, a commonly used amide-type local anesthetic, with perineural dexamethasone for inferior alveolar nerve block in mandibular third molar surgeries. Articaine, known for its rapid onset, strong bone penetration, and reliable anesthetic depth, is particularly well-suited for procedures involving dense mandibular bone. Dexamethasone, a potent glucocorticoid, enhances pain relief and reduces inflammation by inhibiting phospholipase A2 and suppressing pro-inflammatory mediators. A meta-analysis of randomized controlled trials demonstrated that the addition of perineural dexamethasone significantly prolonged postoperative analgesia—by as much as 300 minutes in some cases—and consistently reduced pain scores within the first 24 hours after surgery. Higher doses of dexamethasone (8 mg) produced stronger analgesic effects compared to lower doses (4 mg), suggesting a clear dose-response relationship. Beyond pain management, patients experienced less swelling and trismus, contributing to faster recovery and greater postoperative comfort. Importantly, no adverse effects or neurotoxicity were reported across the included studies, affirming the safety of perineural dexamethasone within therapeutic dosing. The reduced reliance on systemic analgesics and opioids further highlights the multimodal benefits of this approach in minimizing side effects and optimizing recovery. Collectively, these findings support the routine use of perineural dexamethasone as a valuable adjunct to articaine in third molar surgeries, improving anesthesia quality, postoperative outcomes, and patient satisfaction. Future research should aim to standardize dosage protocols, assess long-term safety, and explore broader applications in other dental and surgical contexts.