Intratympanic therapies, usually including glucocorticoid and gentamicin, are becoming worldwide used in clinical practice of Ménière's disease today. However, clinical efficacy and safety of these two therapies are still in controversial.Electronic searches in PubMed, CENTRAL, Web of Science, EMBASE, CINAHL, ClinicalTrials.gov and the European Union Clinical Trials Register were conducted from inception until September 2020.The pre-specified protocol of this systematic review and meta-analysis has been registered and published in November 2018 (PROSPERO Identifier: CRD42018114389). All randomized controlled trials of intratympanic gentamicin or glucocorticoids for Ménière's disease, compared with each other or placebo, were considered for this review.Ten studies with 455 patients met the inclusion criteria. Pooled results indicated significant advantage of intratympanic gentamicin and glucocorticoids over placebo treatments in vertigo control (gentamicin vs placebo: risk rate, RR, 2.56; 95% CI 1.18-5.54; glucocorticoids vs placebo: RR, 3.02; 95% CI 1.36-6.73). There was no significant difference between gentamicin and glucocorticoids in vertigo control (gentamicin vs placebo: RR, 1.18; 95% CI 0.97-1.45). Intratympanic glucocorticoids showed better hearing protective results than gentamicin (change of pure tone audiometric, PTA, mean difference, MD, - 6.48 dB; 95% CI - 11.84 to - 1.13 dB; change of speech discrimination scale, SDS, MD 7.69%; 95% CI 0.83-14.55%).Intratympanic gentamicin and glucocorticoids are two effective approaches to control vertigo symptoms for Ménière's disease. Glucocorticoids showed a potentially better hearing protective role over gentamicin.