Nitrous oxide and midazolam have been used as sedative agents to decrease fear and anxiety associated with dental procedures. Although these agents have been widely used individually, the combination of the two is also commonly used. Four clinical trials were identified that compared the combination technique with the individual use of the drugs. The standardized mean difference (SMD) for each outcome measure was considered for final analysis. Three studies with 534 participants were included in the final meta-analysis, and the SMD [95% CI] was obtained as −0.15 [−0.32, 0.03] and was not statistically significant for cooperation scores. Two studies reported the dose of midazolam required for inducing sedation in 450 participants, and the pooled estimate of SMD [95% CI] was obtained as −0.29 [−0.48, −0.10] and was significant. Two studies with 450 participants reported the time taken to recover from sedation, and the pooled estimate of SMD [95% CI] was obtained as −0.20 [−0.39, −0.01] and favored the combination technique. To conclude, the combination technique combines the pros and cons of both drugs in causing fewer adverse effects due to midazolam by reducing the total dose and also helps to provide better acceptance of nitrous oxide inhalation.