Self-care practices among persons living with type-2 diabetes are very crucial in diabetes manages as poor self-care results in complications. However, little research exists within the Ghanaian context. This study examined whether type-2 diabetes patients' illness perception and diabetes knowledge significantly predict diabetes self-care practices. A cross-sectional survey design was employed and a total of 160 participants (45 males and 115 females) were sampled from a general hospital in Accra. A self-administered questionnaire measuring illness perception, diabetes knowledge and diabetes self-care practices as well as demographic checklist were used collect data. Results showed that illness perception and diabetes knowledge significantly predicted overall diabetes self-care practices. Analysis of domain specific self-care practices showed that patients' diet was significantly predicted by illness perception and diabetes knowledge. Exercise was significantly predicted by only illness perception while blood sugar testing and diabetes foot-care were significantly predicted by diabetes knowledge. Cognitive and emotional representation of diabetes and diabetes knowledge are key determinants of patients' diabetes self-care practices. It is therefore important that appropriate psychosocial interventions are developed to help patients' adherence to recommended self-care practices.