Binge-eating disorder (BED), defined as recurrent episodes of consuming large amounts of food in a short period of time while experiencing a loss of control, remains difficult to manage. Although several pharmacological options are available, they often provide limited long-term benefit and may cause adverse effects. Emerging evidence suggests that gut microbiota dysbiosis contributes to BED pathophysiology. Cytokine infiltration of the gut barrier ultimately causes neuroinflammation, highlighting the gut–brain axis as a potential therapeutic target. This systematic review and meta-analysis evaluated the effectiveness and safety of central nervous system-targeting pharmacotherapies and psychobiotics for BED. Cochrane Library, PubMed, and the Virtual Health Library were searched for randomized controlled trials published from January 2000 to January 2026. Eligible studies evaluated monotherapy with a central nervous system-acting drug or psychobiotics in clinically diagnosed BED populations. Twenty pharmacological trials (n = 2154) and five psychobiotic trials (n = 304) met the inclusion criteria. Risk of bias was assessed using the Cochrane RoB 2 tool, and pooled estimates were calculated using random-effects models. Pharmacological interventions showed a significant pooled effect versus placebo (Standard Mean Difference (SMD) = 0.307, 95% Confidence Interval (CI): 0.103–0.511, p = 0.003), although heterogeneity warrants cautious interpretation. Psychobiotics showed a moderate and significant effect (SMD = 0.680, 95% CI: 0.448–0.913; I² (heterogeneity index) = 0%) and no reported adverse events. Overall, our study implies that psychobiotics may be a safe and potentially effective adjunctive approach for BED, but larger, well-designed trials are needed.