IntroductionThe 2016 WHO antenatal guidelines propose evidence-based recommendations to improve maternal outcomes. We aim to complement these recommendations by describing and estimating the effects of the interventions recommended by WHO on maternal well-being or functioning.Methods and analysisWe will conduct a systematic review of experimental and quasi-experimental studies evaluating women’s well-being or functioning following the implementation of evidence-based antenatal interventions, published in peer-reviewed journals through a 15-year interval (2005–2020). The lead reviewer will screen all records identified at MEDLINE, EMBASE, CINAHL Plus, LILACS and SciELO. Two other reviewers will control screening strategy quality. Quality and risk of bias will be assessed using a specially designed instrument. Data synthesis will consider the instruments applied, how often they were used, conditions/interventions for positive or negative effects documented, statistical measures used to document effectiveness and how results were presented. A random-effects meta-analysis comparing frequently used instruments may be conducted.Ethics and disseminationThe study will be a systematic review with no human beings’ involvement, therefore not requiring ethical approval. Findings will be disseminated through peer-reviewed publication and scientific events.PROSPERO registration numberCRD42019143436.