Abstract Background Poor adherence to the medical regimen is a major clinical problem in the management of patients with diabetes. This study sought to investigate the level of medication adherence to antidiabetic therapy and to identify possible predictors of poor adherence. Methods A hospital based cross-sectional study was conducted from July 2018 to June 2019 among randomly selected follow-up T2D patients at a hospital diabetes clinic. Data were collected through patient interviews, followed by medical chart review. Adherence to antidiabetic therapy that we assessed patients’ responses using validated Brief Medication Questionnaire (BMQ). To identify predictors of poor medication adherence, binary logistic regression analyses were performed using SPSS version 25. Statistical significance was set at p value ≤ 0.05. Results Of the total 357 study participants, 25% were non-adherent to their antidiabetic therapy. Predictors statistically associated with poor adherence were; being female gender (AOR = 1.71, 95% CI 1.01–2.76), and presence of at least one diabetic complication (AOR = 2.02, 95% CI 1.02–3.22). Participants with having at least primary level of education were more likely to adhere to anti-diabetes medication (AOR = 0.42, 95% CI 0.18–0.96). The most common self-reported reasons for non-adherence were forgetfulness, unavailability of medication plus the unaffordability of anti-diabetes medications. Conclusions The proportion of participants’ adherent to anti-diabetes therapies was suboptimal. Being female, the presence of chronic diabetic complications and having no formal education were the main predictors of poor adherence. Strategies that aimed at improving adherence to antidiabetic medications deemed to be compulsory.