To determine whether the association between non-right-handedness and mental problems among adolescents is specific for psychotic symptoms, we included a group of 2096 adolescents with a mean age of 14 years from the general population. Mental health problems were assessed using the parent, self-report, and teacher versions of the Child Behavior Checklist. Internalising problems comprised anxious and depressed, withdrawn and depressed, and somatic complaints. Externalising problems consisted of delinquent behaviour and aggressive behaviour. The remaining problems consisted of social problems, attention problems, and thought problems. The latter were divided into psychotic and non-psychotic items. A total of 14.3% of the adolescents were non-right-handed. We observed positive associations of non-right-handedness with thought problems, social problems, and being withdrawn and depressed. Externalising problems showed no associations with handedness. Within the thought problems subscale, the effect sizes associated with non-right-handedness for psychotic and non-psychotic items were 0.18 (p = .005) and 0.04 (p = .459), respectively. In conclusion, non-right-handedness is predominantly associated with psychosis-related mental problems as early as in adolescence. Handedness could be taken into account when identifying adolescents at risk for psychosis.