Understanding rational numbers is critical for secondary mathematics achievement. However, students with mathematics difficulties (MD) struggle with rational number topics, including fractions, decimals, and percentages. The purpose of this systematic review was to describe the instructional foci of rational number interventions, determine the overall effect size, and explore potential moderators. Forty-three studies were included and 150 effect sizes were meta-analyzed using robust variance estimation. The majority of studies focused on teaching fraction magnitude and arithmetic. An overall effect size of g = 1.02 [0.80, 1.25] was found for rational number interventions favoring treatment conditions over business as usual control. Proximal measures contributed to higher effect sizes than distal measures. Limitations included a high number of fraction interventions contributing to the overall effect size and a large amount of heterogeneity among study effect sizes.