Background Historically, individuals with Down syndrome have been excluded from clinical research. Our objective was to assess the degree of interest adults with Down syndrome have in participating in research from the perspective of the caregivers who care for them. Methods We conducted an online survey of N = 390 caregivers of adults with Down syndrome and asked about interest in research participation and demographics. Results Caregivers were mostly family members, older than 55 years, and White. Caregivers reported that the adult with Down syndrome that they cared for would be more comfortable participating in research that was physiological, such as research involving fit bits (70.2% would participate), exercise (63.3%) or diet apps (53.9%), whereas they would be less likely to participate in clinical trials involving more invasive procedures such as injections (10.9%) and laboratory exams like MRIs (32.0%). We found little difference by age or gender of the adult with Down syndrome or by caregiver education level. Conclusions Our survey identified high interest for less invasive studies, illustrating acceptability of observational and lifestyle studies. More effort may be needed to understand fear and barriers to participation and to create tools and methods to increase interest in more invasive studies.