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Introduction Diabetes distress is a common health problem among people living with type 2 diabetes (T2D), making it difficult to manage the condition. Though it remains a problem, limited attention has been given to the mental health impact it has on people living with the condition.Objective Our study investigated the prevalence and predictors of diabetes distress at a public hospital in the Volta Region of Ghana.Design This was a health facility-based cross-sectional study.Setting Public hospital in the Volta Region of Ghana.Participants 164 people living with T2D at the diabetes clinic.Data collection We collected data using a standardised questionnaire, adopting Diabetes Distress Scale-17 and analysed with descriptive statistics and logistic regression test using STATA V.17.0. Statistical significance was set at a p value <0.05 at 95% CI.Results We found a 43.9% prevalence of diabetes distress, including emotional (58.5%), interpersonal (51.8%), regimen-related (51.2%) and physician-related (12.8%). Those on combined insulin and oral antidiabetic drugs (OADs) had higher odds (adjusted OR=7.26, 95% CI 1.15 to 45.87) of having diabetes distress compared with those on OAD-only regimen.Conclusion The high prevalence of diabetes distress highlights the mental health burden of T2D and gaps in management, a critical factor for poor T2D outcomes. This may decelerate progress towards the achievement of SDG 3.4 aiming to reduce premature mortality from non-communicable diseases through prevention and treatment, and promote mental health and well-being by 2030.