Immaturity in digestive-tract motor function and altered intestinal microbiome may play roles in pathogenesis of infantile colic. We assessed the impact of probiotic therapy on crying duration day, in newborns experiencing colic attacks. The PubMed, Embase, Cinnahl, Web of Science databases, and a clinical trials registry (ClinicalTrials.gov) were searched from inception until 12/02/2020. Random-effects meta-analyses were used to derive standardized mean differences/differences in means and risk ratios. We included 16 studies, which involved 1319 newborns aged up to 6 months. strain DSM17938 was administered predominantly ( = 10). Probiotic intervention reduced the duration of crying (standardized mean difference = -2.012, 95% confidence interval: -2.763 to -1.261, z = -5.25, < 0.0001). The probability of at least a 50% reduction in crying duration was at least 1.98 times higher in the intervention group than in controls (Z = 4.80, < 0.0001). The effects of the intervention were not significantly affected by the risk of bias assessment, percentage of breastfed infants, and duration of the study. In 11 studies, data concerning gut microbiota composition and function and/or immunological markers were given. Probiotics significantly shortened the crying duration, but a causal relationship between the modulatory effect of probiotics on microbiota and the immune system has not been confirmed.