Background: Neonatal jaundice is a transitional phenomenon affecting three out of five full-term newborns globally. Ursodeoxycholic acid could be beneficial in neonatal jaundice needing phototherapy. Methods: We searched PubMed, EBSCO, ProQuest, and Cochrane Library up to August 21st, 2021, for articles to be reviewed. Meta-analysis using random-effects model was performed. Results: Eight studies involving 1116 neonates were chosen in this review; however, only five studies were included for meta-analysis. Phototherapy duration was significantly lower in the interventional group with high heterogeneities. Subgroup analysis of the phototherapy duration based on the risk of bias resulted in a shorter duration (mean difference (MD) = –17.82; 95% CI = –20.17 to –15.47; p = < 0.001) with low heterogeneity in the treatment group. Secondary outcome focusing on mean total serum bilirubin showed a lower mean total serum bilirubin in 48 h post-treatment (MD = –0.43; 95% CI = –0.64 to –0.22; p = < 0.0001) with low heterogeneities in Asian countries.” Conclusions: Ursodeoxycholic acid might be considered as a novel adjuvant therapy in neonatal indirect hyperbilirubinemia to shorten the phototherapy duration and lower the mean total serum bilirubin. © 2022, The Author(s).