Abstract Background In low- and middle-income settings, obtaining informed consent for biobanking may be complicated by socio-economic vulnerability and context-specific power dynamics. We explored participants experiences and perceptions of the research objectives in a community-based multidisease screening and biospecimen collection platform in rural KwaZulu-Natal, South Africa. Methods We undertook semi-structured in-depth interviews to assess participant understanding of the informed consent, research objectives and motivation for participation. Results Thirty-nine people participated (individuals who participated in screening/biospecimen collection and those who did not and members of the research team). Some participants said they understood the information shared with them. Some said they participated due to the perceived benefits of the reimbursement and convenience of free healthcare. Most who did not participate said it was due to logistical rather than ethical concerns. None of the participants recalled aspects of biobanking and genetics from the consent process. Conclusions Although most people understood the study objectives, we observed challenges to identifying language appropriate to explain biobanking and genetic testing to our target population. Engagement with communities to adopt contextually relevant terminologies that participants can understand is crucial. Researchers need to be mindful of the impact of communities’ socio-economic status and how compensation can be potentially coercive.