Background <p>Diabetes-related distress (DRD) is a common psychological response to the demands of managing type 2 diabetes mellitus (T2DM), and it can adversely affect self-care and treatment adherence. However, the burden and determinants of DRD in African populations remain underexplored. This systematic review and meta-analysis aimed to estimate the pooled prevalence of DRD and identify its associated factors among adults with T2DM in Africa.</p> Methods <p>We conducted a systematic search of databases for studies reporting DRD among T2DM in Africa. Eligible studies were screened based on predefined criteria. Statistical analyses were performed using STATA version 14. Heterogeneity was assessed with I² and Cochran’s Q tests; due to substantial heterogeneity, a random-effects model was applied. Publication bias was evaluated using funnel plots and Egger’s test. Subgroup analyses explored variability by country and assessment tool.</p> Results <p>Eleven studies were included in the analysis. The pooled prevalence of DRD was 46.0% (95%CI: 33.9%–58.1%). Emotional burden was the most commonly reported distress domain (58.7%). Subgroup analysis revealed that Sudan had the highest DRD prevalence. Presence of T2DM complications (AOR = 3.55; 95% CI: 2.34–5.37), lack of physical activity (AOR = 2.67; 95% CI: 2.19–3.27), and being married (AOR = 0.37; 95% CI: 0.21–0.65) were significant associated with DRD.</p> Conclusion <p>Nearly half of individuals living with T2DM in Africa experience diabetes-related distress, with emotional and regimen-related concerns being most prevalent. Significant factors such as diabetes complications, physical inactivity, and marital status influence DRD risk, highlighting the need for culturally appropriate psychosocial support integrated into diabetes management strategies across African healthcare settings.</p>