BackgroundChildren of parents with mental disorders have a relatively high risk of developing a mental illness or behavioural disorder. ObjectiveThe aim of this systematic review was to evaluate the efficacy of preventive psychotherapeutic interventions in children of parents with mental illness. In particular, the development of mental illness and/or psychological symptomatology in this population was assessed. MethodThis qualitative systematic review looked at interventions targeting children aged 4-18 years without a diagnosed mental disorder, alone or with their families, with a parent with a diagnosed mental disorder. The protocol was pre-registered in Open Science Framework. A total of 1255 references were retrieved from MEDLINE, PsychArticles, PsycINFO, Springer Link, Science Direct, Scopus and WOS databases, and 12 references from grey literature. This search was replicated by an external reviewer. ResultsFifteen studies involving 1941 children and 1328 parents were included. Interventions were based on cognitive-behavioural and/or psychoeducational components, including six randomized controlled trials. Internalizing symptomatology was assessed in 80% of the studies, externalizing and prosocial behaviour in 47%, and coping style in 33%. Only two studies measured the future risk of developing a mental disorder (ORs of 2.37 and 6.6). There was variability in the format of the intervention (group; family) as well as in the type of intervention and its duration (from one session to 12 sessions). ConclusionsInterventions for children of parents with mental disorder were clinically and statistically significant, especially in preventing internalizing symptomatology at one-year follow-up, with effect sizes ranging from d = -0.28 to 0.57 (95% CI).