Introduction Mental health disorders and low levels of mental well-being can have a lasting effect on life satisfaction and contribution to society for children and adolescents, yet the effectiveness of occupational therapy interventions is unknown. Methods A mixed methods systematic review was conducted including studies with children and adolescents aged 5–16 years, who had mental health difficulties, that evaluated occupational therapy interventions and focused on participation in everyday occupations as an outcome. Results The nine included studies were generally very low quality. The results could not be pooled due to heterogeneity. For children with Asperger’s syndrome, the Cognitive Orientation to Daily Occupational Performance intervention had clinically significant improvements on occupational performance and social skills. For children with attention deficit hyperactivity disorder, the Ultimate Guide to Play, Language and Friendship intervention improved playfulness and the Cognitive–Functional intervention had a statistically significant improvement on occupational performance and behaviour. Conclusion One intervention used by occupational therapists with children with Asperger’s syndrome and two interventions used with children with attention deficit hyperactivity disorder had some evidence of effect. No evidence was identified for the effectiveness of occupational therapy interventions for children and adolescents with other common mental health conditions.