Aims Tailored, patient-centred innovations are needed in the care for persons with type 2 diabetes mellitus (T2DM), in particular those with insufficient glycaemic control. Therefore, this study sought to assess their biopsychosocial characteristics and explore whether distinct biopsychosocial profiles exist within this subpopulation, which differ in health-related quality of life (HRQoL). Methods Cross-sectional study based on data from The Maastricht Study, a population-based cohort study focused on the aetiology, pathophysiology, complications, and comorbidities of T2DM. We analysed associations and clustering of glycaemic control and HRQoL with 38 independent variables (i.e. biopsychosocial characteristics) in different subgroups and using descriptive analyses, latent class analysis (LCA), and logistic regressions. Results Included were 840 persons with T2DM, mostly men (68.6%) and with a mean age of 62.6 (±7.7) years. Mean HbA1c was 7.1% (±3.2%); 308 patients (36.7%) had insufficient glycaemic control (HbA1c>7.0% [53 mmol/mol]). Compared to those with sufficient control, these patients had a significantly worse-off status on multiple biopsychosocial factors, including self-efficacy, income, education and several health-related characteristics. Two ‘latent classes’ were identified in the insufficient glycaemic control subgroup: with low respectively high HRQoL. Of the two, the low HRQoL class comprised about one-fourth of patients and had a significantly worse biopsychosocial profile. Conclusions Insufficient glycaemic control, particularly in combination with low HRQoL, is associated with a generally worse biopsychosocial profile. Further research is needed into the complex and multidimensional causal pathways explored in this study, so as to increase our understanding of the heterogeneous care needs and preferences of persons with T2DM, and translate this knowledge into tailored care and support arrangements.