This study aimed to comprehensively investigate the effects of omega 3 supplementation on BDNF. Original databases were searched using standard keywords to identify all controlled trials that investigating the BDNF effects of omega 3 supplementation. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes. According to the results of a random-effects meta-analysis, omega 3 supplementation significantly raised BDNF levels compared to the control group (pooled WMD of 1.01 μmol/L; 95% confidence interval CI 0.35 to 1.67; P = 0.003) and this increase was even more pronounced for interventions >10 weeks and doses ≤1500 mg/day. Additionally, in individuals under 50 years of age, a greater increase in the effects of omega-3 supplements on this brain factor was observed. The present comprehensive review and meta-regression analysis generally showed that omega-3 supplementation can statistically significantly increase BDNF levels.