Background: Toothbrushing is important for maintaining oral health and preventing periodontal disease. However, the association between toothbrushing and systemic diseases remains unclear in adolescence. In this study, the association between dental self-care (frequency and duration of toothbrushing) and systemic diseases/disorders in adolescents was examined. Methods: We conducted a retrospective review of mandatory medical questionnaires administered during legally mandated freshman medical checkups between 2017 and 2019 at the University of Tokyo, Japan. Out of 9376 total responses, 9098 cases involving individuals under the age of 20 were included in the analysis. Respondents were classified into three groups based on their daily toothbrushing frequency: “1 time or less”, “twice”, and “3 times or more”. For the duration of each toothbrushing session, they were classified into three groups: “1 min or less”, “2–3 min”, and “4 min or more”. A statistical analysis was performed by Pearson’s χ2 test and multinomial logistic regression analysis. Results: Regarding frequency of daily toothbrushing: The χ2 test showed no significant relationship between frequency of toothbrushing and 17 systemic diseases/disorders. A multivariate analysis found that gingival bleeding and sex were independent factors. The risk of gingival bleeding decreased dramatically with increased frequency of toothbrushing (odds ratio (OR): 0.428; 95% confidence interval (CI), 0.366–0.501; p < 0.001). Regarding the amount of time spent on toothbrushing: The χ2 test showed atopic dermatitis and arrhythmia were significantly associated with the duration of toothbrushing (p = 0.032 and p = 0.016, respectively). In the multivariate analysis, atopic dermatitis, gingival bleeding, and sex were independent factors regarding the duration of toothbrushing; longer brushing time was associated with a lower risk of atopic dermatitis (OR: 0.731, 95% CI: 0.578–0.924, p = 0.009) and a lower risk of gingival bleeding (OR: 0.643, 95% CI: 0.567–0.729, p < 0.001). Conclusions: Dental self-care was most strongly associated with gingival bleeding, while the risk of atopic dermatitis was found to increase with shorter toothbrushing times. The results suggest that dental self-care during adolescence is important not only for oral health but also for general health.