ABSTRACT Background: Domperidone and metoclopramide are the most commonly prescribed galactogogues for enhancing milk production, but evidence supporting their efficacy and safety is contradictory. Objectives: To evaluate the efficacy and safety of domperidone and metoclopramide use by breastfeeding women. Search strategy: A systematic literature retrieval of Medline, Embase, Cochrane Library, PubMed, EBSCO, Web of Science, ClinicalTrials.gov and additional bibliography was conducted without time restriction. Selection criteria: Randomised controlled trials exploring the effects of domperidone and metoclopramide in breastfeeding women were included. The primary outcomes were the difference in human milk volume and maternal and neonatal side effects. Data collection and analysis: Two reviewers screened, extracted and assessed the eligible trials independently. Effect size with 95% confidence intervals were presented using random effect model. Main results: Fifteen studies were included. Pooled results demonstrated a low to moderate increase in daily human milk volume of 90.54 mL/day (95%CI 65.69, 115.39), 0.04 mL/day (95%CI 28.85, 28.93) with the use of domperidone and metoclopramide, respectively. No differences were noted in the incidence of maternal side effects with domperidone (RR1.20, 95%CI 0.74, 1.97) or metoclopramide (RR1.23, 95%CI 0.51, 2.94). Additionally, there were no significant differences in the volume of human milk and maternal side effects between the domperidone and metoclopramide group. Conclusions: Domperidone demonstrated a modest increase of 90.54 mL/day in milk production, and had a lower risk of side effects in mothers and infants, which could be considered as a suitable choice for breastfeeding women. Keywords: domperidone; metoclopramide; galactogogues; human milk; side effects