The addition of adjuvants to local anesthetics in brachial plexus block enhances the efficacy of the nerve blockade. Dexamethasone and Clonidine are commonly used adjuvants with distinct mechanisms of action. This study aims to compare these adjuvants in terms of onset of action, duration of analgesia, hemodynamic stability, and adverse effects when used with Bupivacaine and Lignocaine with Adrenaline in an interscalene brachial plexus block. The findings will provide insight into selecting the optimal adjuvant for prolonged postoperative analgesia. Materials and Methods: This prospective, randomized, double-blind, comparative clinical study was conducted in the Department of Anaesthesia Shadan Institute of Medical Sciences, Teaching Hospital & Research Centre after obtaining ethical committee approval and written informed consent from all patients.The participants were divided into two groups: Group D (Dexamethasone) and Group C (Clonidine). The onset time, duration of analgesia, hemodynamic stability, and adverse effects were analyzed. Results: Group D (Dexamethasone) had a slightly faster onset of sensory and motor blockade (12.3 ± 2.1 min) compared to Group C (Clonidine, 13.0 ± 2.3 min), but the difference was not statistically significant (p > 0.05). Dexamethasone significantly prolonged analgesia (780 ± 50 min) compared to Clonidine (610 ± 45 min), with p < 0.05 (statistically significant). Excellent satisfaction was higher in Group D (85%) compared to Group C (72%), suggesting that patients experienced better pain relief and comfort with Dexamethasone. Fewer patients rated their satisfaction as "Fair" in the Dexamethasone group (3%) compared to Clonidine (8%), further supporting its superior efficacy in pain management. Conclusion: Dexamethasone provides a longer duration of analgesia than Clonidine when used as an adjuvant in interscalene brachial plexus block, making it a preferred choice in clinical settings requiring prolonged postoperative analgesia.