Background: Current era of minimally invasive surgery and awake craniotomy has created revived attention towards scalp blocks and its benefits. Present study was conducted to evaluate and compare effects of dexmedetomidine and clonidine as an adjuvant to bupivacaine in scalp block for supratentorial craniotomy surgery. Methods: The prospective, comparative, randomized study was conducted by Department of Anaesthesia at J.J. Hospital and Grant Medical College, Mumbai, India. Data was collected between September 2018 to August 2020. Adult subjects between 18 years and 60 years (both inclusive) of either gender with ASA-I, Glasgow Coma Scale (GCS) of 15, and indicated to undergo supratentorial craniotomy surgeries were enrolled. One study group received 1 mcg/kg Clonidine, while other 1 mcg/kg Dexmedetomidine, both diluted with normal saline. Hemodynamic parameters, analgesic requirement and Ramsay Sedation score (RSS) were assessed. Results: 60 patients (30 in each group) were enrolled. Mean age, baseline weight, gender distribution and duration of surgery were statistically comparable between study groups (P>0.05). Mean blood pressure, mean arterial pressure and heart rate were significantly higher in the clonidine group at the time of pin insertion, incision and during most of the intraoperative period (p<0.05). RSS was comparable between study groups at all time-points (p>0.05). Analgesic requirement was overall higher in clonidine group, indicating better analgesia with Dexmedetomidine. Conclusion: Dexmedetomidine led to lesser vascular parameters changes, with lower analgesic requirement versus clonidine however, sedation scores were comparable.