Background: Among child and adolescent patients, persistent but untreated malocclusions may or may not have psychological and social impacts on the individual's quality of life. Objectives: To gain knowledge of malocclusions and its impact on oral health-related quality of life (OHRQOL), we conducted a systematic review of quantitative studies for evidence regarding the influence of malocclusions on OHRQOL in children and adolescents. Materials and methods: Five databases (MEDLINE via PubMed, EMBASE, Psychinfo, CINAHL, and the Cochrane Library) were searched using specified indexing terms. The following inclusion criteria were used: child or adolescent study population; healthy study participants without syndromes such as cleft lip/palate or severe illness; no previous or ongoing orthodontic treatment among participants; a focus on malocclusions and quality of life; controlled or subgrouped according to malocclusions/no malocclusions; malocclusions and/or orthodontic treatment need assessed by professionals using standardized measures; self-assessed OHRQOL estimated using validated questionnaire instruments; full-text articles written in English or Scandinavian languages. Quality of evidence was classified according to GRADE guidelines as high, moderate, or low. Results: The search produced 1142 titles and abstracts. Based on pre-established criteria, the full-text versions of 70 articles were obtained, 22 of which satisfied the inclusion criteria. After data extraction and interpretation, six publications were deemed eligible for full inclusion. All six were of cross-sectional design, and the quality of evidence was high in four cases and moderate in the remaining two. The four studies with a high level of quality reported that anterior malocclusion had a negative impact on OHRQOL, and the two with a moderate level of quality reported that increased orthodontic treatment need had a negative impact on OHRQOL. Conclusion: The scientific evidence was considered strong since four studies with high level of quality reported that malocclusions have negative effects on OHRQOL, predominantly in the dimensions of emotional and social wellbeing.