Background <p>Despite an increase in the incidence of kidney failure in Morocco, treatment with transplantation remains limited. Exploring the perspectives of individuals with kidney failure toward kidney transplantation is essential, as it can provide information on previously unknown barriers to care, guide public health efforts, and inform patient-provider conversations. The aim of this study was to identify knowledge, perceptions and willingness to undergo kidney transplantation among individuals with dialysis -dependent kidney failure in southern Morocco.</p> Methods <p>This was a cross-sectional observational study with quasi-qualitative data conducted across seven hemodialysis centers (six urban centers and one rural center). Participant responses were collected via a face‒to‒face questionnaire and open‒ended questions from September to December 2021. The study was approved by the ethics committee located in Marrakech.</p> Results <p>Three hundred twenty-two individuals (178 men (55.3%) and 144 women (44.7%), mean age of 53.7 [17.9] years, and mean years on dialysis of 6.12 [5.3] years) participated. Fifty-four (54.7%) participants reported a lack of knowledge regarding kidney transplantation. Those who reported a lack of knowledge were more likely to have no education (AOR = 4.05, CI 95% [1.64-10.00]) or primary level education (AOR = 2.85, CI 95% [1.36-6.00]), receiving dialysis in a private center (AOR = 8.95, CI 95% [4.35–18.39]) and not having a potential donor (AOR = 5.56, CI 95% [2.14–14.42]). Approximately two-thirds (64.9%) expressed their willingness to undergo kidney transplantation. The predictive factors of this willingness included younger age (AOR = 3.54, CI 95% [1.66–7.53]) and perceived improvement in quality of life from transplantation compared with hemodialysis (AOR = 12.89, CI 95% [5.88–28.21]). The barriers to accepting kidney transplantation were fear of complications, lack of information and religious reasons. Additionally, 72.7% (<i>n</i> = 234) and 70.2% (<i>n</i> = 226) of the participants believed that the Islamic religion is accepting of kidney donation from living or deceased donors, respectively, whereas 20% (<i>n</i> = 65) were unsure of Islam’s role as it relates to kidney transplantation.</p> Conclusions <p>Significant gaps in patient knowledge about kidney transplantation were highlighted in this study. Despite this, a high proportion of patients expressed their willingness to undergo surgery, underscoring the importance of targeted and culturally adapted patient education to support informed decision-making.</p> Trial registration <p>Clinical trial number: Not applicable.</p>