To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], −1.61; 95% confidence interval [95% CI], −2.44 to −0.79;
p
< 0.001), attention deficit hyperactivity disorders (SMD, −0.39; 95% CI, −0.78 to −0.00;
p
= 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, −0.86; 95% CI, −1.48 to −0.24;
p
= 0.006) compared with control group, but showed no difference between depression group (SMD, −0.06; 95% CI, −0.15 to 0.03;
p
= 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63−0.98;
p
= 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69−0.99;
p
= 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.