Aims To describe self-care as defined by the Middle Range Theory of Self-Care of Chronic Illness and to identify clinical and socio-demographic determinants in a T2DM population. Methods A multicentre observational cross-sectional study was conducted involving 540 adults with a confirmed diagnosis of T2DM from six outpatient diabetes services in Italy. Socio-demographic and clinical data were collected from medical records. The Self-Care of Diabetes Inventory (SCODI) was used to measure self-care maintenance, monitoring, management, and confidence dimensions. For each separate scale, scores were standardized 0–100 with higher SCODI scores indicating better self-care; a score ≥ 70 is adequate. Multiple quantile regression models were performed to identify determinants of each self-care dimension. Results Self-care maintenance (median = 81.3) and self-care confidence (median = 79.5) were adequate in most of the subjects. Self-care monitoring was adequate in only half of the sample (median = 70.6). Self-care management was poor (median = 59.4). Lower self-care maintenance was associated with lower self-care confidence (p < 0.001). Lower self-care monitoring was associated with being male (p < 0.001), having lower self-care confidence (p < 001), and having diabetes for < 10 years (p < 0.001). Lower self-care management was associated with being male (p = 0.002), being older (p = 0.005), having a low income (p = 0.030), being employed (p = 0.008), having missed diabetes education in the last year (p = 0.002), and lower self-care confidence (p < 0.0001). Lower self-care confidence was associated with having diabetes for < 10 years (p = 0.008), and having at least one comorbid condition (p = 0.006). Conclusions Determinants of self-care maintenance, monitoring, management and confidence include both clinical and socio-demographic variables. Modifiable determinants such as self-care confidence and diabetes self-care management education could be used to tailor interventions to improve diabetes self-care.