Purpose: Weight gain associated with antipsychotics in schizophrenia has been an ongoing concern. This meta-analysis examined the efficacy and safety of amantadine as an adjunctive treatment of weight gain in schizophrenia by systematically searching and analyzing randomized controlled trials (RCTs). RCTs comparing adjunctive amantadine with placebo in adult patients with schizophrenia were included in the meta-analysis. Methods: Two independent investigators searched the literature and extracted data. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio +/- 95% confidence intervals were calculated. Results: Five RCTs (n = 265) with double-blinded design lasting 8.2 +/- 5.9 weeks were included in the analysis. Amantadine outperformed placebo regarding weight reduction with moderate effect size (trials, 3; n = 205; WMD -2.22 kg; P = 0.001, I-2 = 45%). Amantadine also outperformed placebo at endpoint in the negative symptom (the Positive and Negative Syndrome Scale [PANSS] [1 trial] and the Scale for the Assessment of Negative Symptoms [1 trial]) scores (trials, 2; n = 84; SMD, -0.56; P = 0.01, I-2 = 12%), but not in the PANSS total scores (trials, 2) (SMD, -0.31; P = 0.16, I-2 = 0%) and the positive symptom (PANSS [1 trial] and the Scale for the Assessment of Positive Symptoms [1 trial]) scores (SMD, 0.13; P = 0.54, I-2 = 0%). Except for insomnia (P = 0.007; number needed to harm, 6; 95% confidence interval, 4-16), all-cause discontinuation (risk ratio, 1.12; P = 0.54, I-2 = 0%) and other adverse events were similar between the amantadine and placebo groups. Conclusions: According to this meta-analysis of 5 RCTs, adjunctive amantadine seems to be an effective option for attenuating antipsychotic-related weight gain in patients with schizophrenia. More RCTs are needed to inform clinical recommendations.