The twin challenges of lack of access to improved sanitation and food insecurity remain critical, particularly in the global south. With cognizance of the nutrient potential of human excreta, there has been increasing interest in linking sanitation innovations with agriculture by using nutrients recovered from human excreta for crop production, thus, closing the nutrient loop. While studies and field trials have explored and validated the technical feasibility of reusing nutrients recovered from human excreta in agriculture, there is still limited knowledge of its social acceptability. This study examined whether indigenous knowledge can be leveraged to increase the acceptability of human-excreta-derived plant nutrient sources such as treated effluent in agriculture. A qualitative research design comprising seven focus group interviews (five in rural areas and two in peri-urban areas) was conducted in KwaZulu Natal, South Africa. Findings from the focus groups reveal a willingness to grow and consume food using treated effluent. Additionally, participants made references to indigenous practices that encourage recycling and reuse of human excreta. Given the potential to simultaneously address issues of food insecurity and sanitation that characterize many peri-urban and rural areas in South Africa, we recommend further studies in this area.