Binge-Eating Disorder (BED) is the most common eating disorder in the United States. Lisdexamfetamine (LDX) was approved in 2015 by the FDA for treatment of BED and is the only drug approved for treating the disorder. There has been no systematic evaluation of the published clinical and preclinical evidence for efficacy of LDX in treating BED and the mechanisms responsible for the therapeutic action of the drug. To address this gap, we conducted a systematic review and meta-analysis using PRISMA guidelines. Fourteen clinical and seven preclinical articles were included. There is consistent evidence from clinical studies that LDX is an effective treatment for BED and that the drug reduces the BED symptoms and body weight of patients with the disorder. There is also consistent evidence from preclinical studies that LDX reduces food intake but no consistent evidence for a preferential reduction of palatable food consumption by the drug in rodents. The evidence on mechanism of action is more limited and suggests LDX may reduce binge eating by a combination of effects on appetite/satiety, reward, and cognitive processes, including attention and impulsivity/inhibition, that are mediated by catecholamine and serotonin mechanisms in the brain. There is an urgent need for adequately powered, placebo-controlled, behavioural and neuroimaging studies with LDX (recruiting patients and/or individuals with subclinical BED symptoms) to further investigate the mechanism of action of the drug in treating BED. An improved understanding of the behavioural and neurochemical mechanisms of action of LDX could lead to the development of improved drug therapies to treat BED.