The sedation outcomes associated with dexmedetomidine compared with those of propofol during drug-induced sleep endoscopy (DISE) remains unclear. Electronic databases (i.e., the Cochrane controlled trials register, Embase, Medline, and Scopus) were searched from inception to 25 December 2020 for randomized controlled trials (RCTs) that evaluated the sedation outcomes with dexmedetomidine or propofol in adult patients diagnosed with obstructive sleep apnea (OSA) receiving DISE. The primary outcome was the difference in minimum oxygen saturation (mSaO2). Five RCTs (270 participants) published between 2015 and 2020 were included for analysis. Compared with dexmedetomidine, propofol was associated with lower levels of mSaO2 (mean difference (MD) = −7.24, 95% confidence interval (CI) −12.04 to −2.44; 230 participants) and satisfaction among endoscopic performers (standardized MD = −2.43, 95% CI −3.61 to −1.26; 128 participants) as well as a higher risk of hypoxemia (relative ratios = 1.82, 95% CI 1.2 to 2.76; 82 participants). However, propofol provided a shorter time to fall asleep and a lower risk of failed sedation compared with dexmedetomidine. No significant difference was found in other outcomes. Compared with propofol, dexmedetomidine exhibited fewer adverse effects on respiratory function and provided a higher level of satisfaction among endoscopic performers but was associated with an elevated risk of failed sedation.