Background: We identified participant-level risks and safeguards in social-behavioural research with adults with developmental disabilities. Method: We conducted a qualitative systematic review on risks and safeguards in peer-reviewed research with adults with developmental disabilities. We identified research reporting on risks and safeguards published between 2009 and 2023 by searching eight databases and conducting hand searches of reference lists. We conducted thematic analysis using independent data extraction and coding, and investigator triangulation. Results: From 23 manuscripts, we identified: (1) risks associated with research participation of adults with developmental disabilities (e.g., physical, relational, psychological, and social risks as well as a loss of privacy and confidentiality) and (2) safeguards (e.g., using guiding frameworks, reducing participant burden, securing privacy and confidentiality, and fostering psychological and relational well-being). Conclusions: We encourage researchers to foster positive experiences so research participants feel valued and respected, and enjoy having the experience and opportunity to contribute to scientific discoveries.