Background: Reversing left ventricular hypertrophy (LVH) can reduce the incidence of adverse cardiovascular events. The lack of direct comparison between different antihypertensive drugs cannot evaluate the superiority-inferiority differentiation of different antihypertensive drugs in reversing LVH. Therefore, the objective of this protocol for systematic review and meta-analysis was to compare the efficacy of different types of antihypertensive drugs in reversing LVH in hypertensive patients. Methods: This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. Studies were identified through systematic searches in June 2021 with no restrictions on date and time, language, and publication status using the following bibliographic databases: Embase, Medline, PubMed, Web of Science, Science Direct, and the Cochrane Library. The risk of bias assessment of the included studies was performed by two authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). All calculations were carried out with Stata 11.0 (The Cochrane Collaboration, Oxford, United Kingdom). Results: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. Conclusion: We hypothesized that the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in antihypertensive therapy could achieve better efficacy in reversing LVH in hypertensive patients.