IntroductionTherapeutic management of neonatal pain is essential to reduce changes in initial and subsequent development. Although glucose has been shown to be effective in relieving pain, concentrations and dosages remain to be standardised. The objective of this systematic review and meta-analysis is to identify the efficacy of glucose as an analgesic in preterm infants.Methods and analysisThe Web of Science, Science Direct, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, PubMed, Medline, Latin American and Caribbean Health Sciences Literature and Embase databases will be researched for randomised studies published until December 2021. This systematic review and meta-analysis will include studies investigating the use of glucose for pain control in premature neonates. The primary outcome will be pain relief. Three independent reviewers will select the studies and extract the data from original publications. The risk of bias was assessed using the Cochrane risk of bias tool. Data synthesis will be performed using the Review Manager software (RevMan V.5.2.3). We will evaluate heterogeneity based on I²statistics. In addition, quantitative synthesis will be performed if the included studies are sufficiently homogeneous.Ethics and disseminationEthical approval for the research will not be required for this systematic review. The results of this study will be published in an international journal.Trial registration numberThis protocol was submitted to the International Prospective Register of Systematic Reviews (PROSPERO, number CRD42021236217).