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This study aimed to investigate the impact of hypogonadism on bone mineral density (BMD) in children and adolescents with chronic diseases to determine the relationship between sex hormones and BMD. This retrospective study included 672 children and adolescents with chronic diseases such as hemato-oncologic, rheumatoid, gastrointestinal, and endocrinologic diseases. The relationship between the sex- and Tanner-stage-matched <i>Z-scores</i> for sex hormones and the sex- and age-matched lumbar spine BMD (LSBMD) <i>Z-scores</i> was evaluated. Adjustments were made for confounders such as underlying diseases, age at diagnosis, and age- and sex-matched body mass index <i>Z-scores</i>. Patients had a mean LSBMD <i>Z-score</i> of −0.55 ± 1.31. In the multivariate regression analysis, male testosterone showed a positive association with the LSBMD <i>Z-score</i> (<i>p</i> < 0.001), whereas female estradiol, luteinizing hormone, and follicular-stimulating hormone showed no significant association with the LSBMD <i>Z-scores</i>. In the male group, the testosterone level was associated with LSBMD <i>Z-scores</i> > −1.0 (<i>p</i> < 0.001), > −2.0 (<i>p</i> < 0.001), and > −3.0 (<i>p</i> = 0.002), while the estradiol level was associated with LSBMD <i>Z-scores</i> > −2.0 (<i>p</i> = 0.001) and > −3.0 (<i>p</i> = 0.002) in the female group. In conclusion, sex hormones are associated with BMD in children and adolescents with chronic diseases. Therefore, various measures may be necessary to predict future skeletal problems and improve bone health in these patients.