Background: Previous studies in Nigeria reveal a significant knowledge gap about neonatal jaundice (NNJ) among pregnant women, despite improvements in antenatal care (Adeleye et al., 2020; Adediran et al., 2021). Targeted health education is crucial for enhancing awareness and improving early detection and management of NNJ. Therefore, the objective of this research is to evaluate the effectiveness of the interaction of health education in enhancing the knowledge of pregnant women in Kwara State, Nigeria, regarding the signs, causes, complications, and management of neonatal jaundice. Methodology: This study utilized a quasi-experimental design to investigate the causal relationship between health education and knowledge of neonatal jaundice (NNJ) management among pregnant women in Ilorin, Kwara State. The population included pregnant women in their third trimester attending antenatal clinics, with specific inclusion and exclusion criteria. A total sample of 128 participants was divided into intervention and control groups. Data were collected using a structured questionnaire, ensuring reliability through test-retest methods. Analysis employed SPSS, using descriptive and inferential statistics, with significance set at p<0.05, providing valuable insights into maternal health practices. Results: The analysis indicated no statistically significant difference in baseline knowledge mean scores between the two groups (t(126) = 0.864, p = 0.39). However, following the intervention, the experimental group demonstrated significantly higher knowledge scores compared to the control group (t(126) = 9.05; p = 0.0001). Correlation analysis revealed a significant relationship between mothers' management of neonatal jaundice (NNJ) and knowledge of its causes (r = -0.393; p = 0.001), but no significant correlations with knowledge of signs (r = -0.131; p = 0.302) or complications (r = -0.190; p = 0.133) of NNJ post-intervention. At the pre-intervention phase, the standardized coefficient (R) for knowledge on neonatal jaundice (NNJ) management was 0.077 (p = 0.545), indicating a weak relationship. The R-square value of 0.006 (0.6%) suggested minimal impact on management. Post-intervention, R increased to 0.290 (p = 0.02), with an R-square of 0.084 (8.4%), showing that increased knowledge significantly improved NNJ management. Conclusion: In conclusion, the study shows that educational interventions significantly increased neonatal jaundice knowledge among the intervention group. Maternal knowledge positively influences NNJ management, highlighting the need for ongoing health education and public awareness campaigns to improve neonatal health outcomes in Kwara State, Nigeria.