Objectives: To determine the strength of evidence for commonly used interventions for colic in breast-fed and mixed-fed infants younger than 6 months. Methods: Searches of PubMed, CINAHL, Embase, AMED, and Web of Science databases were conducted from July 2014 to July 2015. Included studies were randomised controlled trials involving mothers and their colicky infants younger than 6 months; assessed colic against the Wessel or modified Wessel criteria; and included phytotherapies, prescription medicines, and maternal dietary interventions. Studies with <16 participants were excluded. Meta-analyses were conducted where data were sufficient to enable pooling. Quality was assessed against the Cochrane Risk Bias Assessment Tool. Results: A total of 17 articles met the inclusion criteria for this review. The 6 studies included for subgroup meta-analysis on probiotic treatment, notably Lactobacillus reuteri, demonstrated that probiotics appear an effective treatment, with an overall mean difference in crying time at day 21 of -55.8 min/day (95% CI -64.4 to -47.3, P=0.001). The 3 studies included for subgroup meta-analysis on preparations containing fennel suggest it to be effective, with an overall mean difference of -72.1 min/day (95% CI -126.4 to -17.7, P<0.001). Conclusions: Probiotics, in particular L reuteri, and preparations containing fennel oil appear effective for reducing colic, although there are limitations to these findings. The evidence for maternal dietary manipulation, lactase, sucrose, glucose, and simethicone is weak. Further well-designed clinical trials are required to strengthen the evidence for all of these interventions.