The parasitic mite Varroa destructor is a sanitary threat to beekeeping and causes significant losses in honey bee colonies. Thus, different acaricides have been applied as a strategy to control this disease. In the context of Integrated Pest Management, acaricides based on natural compounds, such as organic acids and essentials oils, are chosen by beekeepers to minimize negative effects on colonies and hive products. Considering the variety of natural active ingredients reported to have varroacidal activity and their different application systems, the aim of this work was to synthesize and quantify scientific knowledge on the acaricide performance of natural compounds to control V. destructor populations in Apis mellifera colonies. A systematic revision and a meta-analysis on the percentage of efficacy published for these formulations were conducted by selecting articles published between 2002 and 2022. According to our results, most publications investigated the efficacy of natural compounds in temperate climates and in European honey bee colonies since Varroa control is practically compulsory under these conditions. Thymol (THY) showed higher estimated efficacy compared to oxalic and formic acids (FA) and other essential oils (EOs). Variable efficacies were found in colonies treated with the natural compounds considered in this study according to different doses and application methods. The high between-study heterogeneity found in this revision might be explained by several factors, including the number of colonies and intra-apiary variation. As such, standardized protocols for field assays are key to improving efficacy evaluation. In addition, methodological implications are discussed.