Background <p>Maintaining hemodynamic stability during craniotomy is essential to prevent elevated intracranial pressure and related complications. Regional blocks, including sphenopalatine ganglion (SPG) block and scalp block, may stabilize hemodynamics, but comparative evidence is limited. This study systematically evaluated the efficacy and safety of SPG block versus scalp block in adults undergoing craniotomy.</p> Methods <p>This systematic review and meta-analysis adhered to the PRISMA guidelines. We searched PubMed, CENTRAL, Scopus, and EBSCO (2010–2025). Eligible studies were randomized controlled trials (RCTs) comparing SPG block with scalp block in adult craniotomy patients. Primary outcomes were intraoperative MAP and HR. Secondary outcomes included intracranial pressure (ICP), postoperative pain, opioid use, and complications. Data were synthesized using random-effects meta-analysis.</p> Results <p>Five RCTs (<i>n</i> = 285) were included. No significant differences in MAP or HR were observed in the SPG block group compared with the control group at all measured time points, including post–pin insertion, post–skin incision, and post–dural incision. (peak MAP = -0.01 [-0.12–0.09]; cumulative MAP = 0.00 [-0.14–0.13]; peak HR = -0.05 [-0.16–0.06]; cumulative HR = -0.09 [-0.19–0.02]). Secondary outcomes suggested SPG block may lower ICP, improve brain relaxation, and reduce postoperative pain and opioid requirement with minimal complications.</p> Conclusion <p>Both SPG block and scalp block maintained intraoperative hemodynamic stability. However, SPG block demonstrated additional advantages, including improved postoperative analgesia, lower intracranial pressure, and enhanced brain relaxation, while remaining a simple and noninvasive technique with minimal adverse effects. Evidence is limited by small sample sizes, highlighting the need for larger, standardized trials to confirm these findings.</p> Trial registration <p>PROSPERO ID: CRD420251131959.</p>