This was a systematic review of studies examining the effect of COVID-19 on the health-related quality of life (HRQoL) of children and adolescents. The review was conducted by examining the current literature and analyzing up-to-date evidence. The studies were extracted from three major databases (CINAHL Complete, MEDLINE, and Web of Science) and analyzed. Studies on children and adolescents whose HRQoL has been affected by COVID-19 were included based on the eligibility criteria. Ultimately, eight studies met these criteria. The evidence of the selected studies was analyzed; the research design, age categories, respondents, evaluation tools, gender differences, and variability before and during COVID-19 were systematically reviewed. This review found differences in these groups regarding oral symptoms, functional limitations, emotional well-being, and social well-being. Furthermore, this review highlighted the relative paucity of studies that comprehensively investigate the latest evidence of changes in the HRQoL of children and adolescents due to COVID-19 in preparation for the post-COVID era.