Necrotizing enterocolitis (NEC) remains a major cause for neonatal mortality and morbidity in preterm infants. The purpose of this review was to summarize evidence from systematic reviews of randomized-controlled trials (RCTs) regarding antenatal and postnatal interventions for preventing NEC. PubMed, EMBASE, the Cochrane Library Databases, Database of Abstracts of Reviews of Effects, and Campbell Library were searched for meta-analyses in which NEC was reported as an outcome after antenatal or postnatal strategies. The AMSTAR instrument was used to evaluate quality of included reviews. Grading of Recommendations, Assessment, Development and Evaluation assessment was used to evaluate certainty of evidence. We identified 98 meta-analyses of RCTs. The quality of included reviews was adequate, whereas the certainty of evidence was moderate to very low. Moderate certainty evidence showed a reduction in NEC following administration of a combination of species of probiotics, probiotics (any), antenatal corticosteroids in pregnant women at risk of preterm birth, and ibuprofen versus indomethacin for treatment of patent ductus arteriosus (PDA). For surgical NEC, moderate certainty evidence showed an increased risk with lower (85–89%) oxygen saturation target levels, compared with higher (91–95%) oxygen saturation target levels. In conclusion, decreased risk of NEC is observed with probiotics, antenatal corticosteroids for women at risk of preterm birth, and ibuprofen versus indomethacin for treatment of PDA. Targeting lower oxygen saturations may increase the risk of surgical NEC, compared to targeting higher saturations.