Introduction: Add-on magnesium sulfate (MgSO4) for refractory asthma exacerbation has been much debated. The aim of this review and meta-analysis is, therefore, to provide an update on the current evidence for the efficacy of MgSO4 in exacerbations of asthma in adults refractory to standard of care treatment. Methods: A systematic review was performed in accordance with the PRISMA guidelines. The search was performed in the PubMed database (updated April 2023). For the meta-analysis, a random-effects model was applied using the metaphor package for RStudio (RStudio, Inc.). Results: A total of 17 randomized controlled trials were included. Three of the nine studies addressing treatment with intravenous (IV) MgSO4 found a significant effect on lung function compared to placebo. Of the eight studies investigating hospital admission rate, only two found a significant effect of MgSO4. Six of the nine studies investigating treatment with nebulized MgSO4 compared to placebo found a favorable effect on forced expiratory volume in 1. second (FEV₁) and peak expiratory flow rate (PEF). Only two of the five studies investigating the effect on hospital admission rate found an effect of MgSO4. Comparing effect sizes in a meta-analysis revealed a greater effect on PEF in asthma patients treated with nebulized MgSO4 (MD, 23.57; 95% CI, −2.48 to 49.62, p < 0.01) compared to placebo. The analysis of patients treated with i.v. MgSO4 compared to placebo showed no statistically significant difference (MD, 5.49; 95% CI, −18.67 to 29.65, p = 0.10). Conclusion: Up to two out of three studies revealed an effect of MgSO4 treatment for asthma exacerbation when assessed by FEV₁/PEF, but fewer studies were positive for the outcome of hospital admissions.