Purpose: This study compared the prevalence of hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) between transgender and gender-diverse (TGD) individuals and cisgender individuals. Methods: We conducted a retrospective analysis using a large electronic health record database spanning 2004–2024. TGD individuals were identified using International Classification of Diseases, Tenth Revision codes related to gender identity and stratified by hormone therapy status. Cisgender comparison groups were defined by the absence of gender identity diagnoses and hormone therapy exposure. Prevalence odds ratios (ORs) with 95% confidence intervals were calculated to compare hEDS and HSD diagnoses between groups. Results: TGD individuals demonstrated a significantly higher prevalence of hEDS and HSD than cisgender individuals (OR: 18.45). The prevalence among TGD individuals assigned female at birth was 2.62%, and among those assigned male at birth, 1.00%, compared with 0.16% and 0.04% in cisgender females and males, respectively. Hormone therapy status was not associated with significant differences in prevalence. Conclusions: These findings indicate a substantially increased burden of hypermobility-related disorders among TGD individuals. Enhanced clinical recognition and multidisciplinary management strategies are needed to address the unique health care challenges faced by this population.