Despite the availability of effective, safe, and feasible pain management strategies, infant pain remains undertreated. Parents can play a key role in advocating for or delivering pain management strategies if they are educated. To date, a quantitative synthesis of the effectiveness of parental education about pain management in the neonatal period has not been performed. To systematically review the effectiveness of parental education during the neonatal period on pain management in infancy. MEDLINE, EMBASE, PsycInfo, CINAHL, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) and non-randomized trials (NRTs) that evaluated parental education with respect to pain management during the neonatal period in any setting from inception to February 2021. Screening of article titles and abstracts and data extraction were performed in duplicate. The risk of bias was assessed using the Cochrane Risk Bias Tool 2.0 and the Risk of Bias in Non-randomized Studies of Interventions for RCTs and NRTs, respectively. As per the GRADE methodology, critically important and important outcomes were identified. Critically important outcomes included utilization of pain management strategies and infant pain. Important outcomes included parental knowledge about pain mitigation strategies, parental attitudes, compliance with painful procedures, procedure outcomes, and safety. Data were combined and presented as relative risk (RR) or mean or standardized mean difference (MD or SMD) with 95% confidence interval (CI). Of the six studies eligible for inclusion, four studies were RCTs and two studies were NRTs. Written information and/or video were used to deliver parental education during the neonatal period in hospital settings in all studies. Four studies (two RCTs and two NRTs) reported on critically important outcomes. The risk of bias was low for the two RCTs and moderate to serious for the two NRTs. Utilization of pain management strategies was assessed for heel lance in the first 48 hours of life in two studies and for vaccine injection at 2 to 6 months of life in two studies. Higher utilization rate for pain management strategies was reported in the pain education group in three studies (RR 1.15, 95% CI 1.04, 1.26; N=2712). There was no difference in the mean number of pain management strategies used in one NRT tracking utilization tracking utilization as continuous data (MD 0.20, 95% CI -0.01, 0.41; N=178). Parent-reported infant pain scores were lower in the pain education group in one RCT (MD -0.16, 95% CI -0.27, -0.06; N=1615). The quality of evidence for the outcome of utilization of pain management strategies was very low while for the outcome of infant pain the quality of evidence was moderate. Five studies (3 RCTs and 2 NRTs) reported on important outcomes. The risk of bias was low for two RCTs and high for one RCT and moderate to serious for the two NRTs. Parental knowledge about pain management strategies (SMD 0.54, 95% CI 0.26, 0.82), parental confidence in their ability to manage pain (SMD 0.24, 95% CI 0.14, 0.34), parental satisfaction with education (MD 1.18, 95% CI 0.84, 1.52) and parental satisfaction with pain management (RR 1.05. 95% CI 1.01, 1.08) were increased in the pain education group. None of the included studies reported on procedural outcomes. No adverse events with the pain education nor the use of pain management interventions were reported in one study. Parental education in the neonatal period was effective in increasing utilization of pain management strategies during painful procedures. Reduction of pain in infants is based on one study of moderate quality. Furthermore, parental education increased parental knowledge about pain management strategies, confidence in their ability to manage infant pain, and satisfaction with the education and pain management. Parental pain education should be incorporated into postnatal care.