Background: Type 2 diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia that may lead to various complications and reduced quality of life. Psychological factors, particularly diabetes-related distress, and behavioral factors such as self-care play important roles in influencing patients' quality of life. Objective: To examine the relationship between diabetes-related distress and self-care with the quality of life among patients with type 2 diabetes mellitus at Bulu Lor Primary Health Center, Semarang, Indonesia. Methods: A quantitative cross-sectional study was conducted among 75 patients with type 2 diabetes mellitus selected using purposive sampling. Data were collected in April 2025 using the Diabetes Distress Scale (DDS), Summary of Diabetes Self-Care Activities (SDSCA), and Diabetes Quality of Life (DQOL) questionnaire. Data were analyzed using the Spearman rank correlation test. Results: Most respondents were aged ≥60 years (85.3%), female (65.3%), and had completed primary school education (34.7%). Diabetes-related distress was moderately and negatively correlated with quality of life (r = −0.432; p < 0.001), indicating that higher diabetes-related distress was associated with lower quality of life. Self-care showed a moderate positive correlation with quality of life (r = 0.476; p < 0.001), indicating that better self-care was associated with higher quality of life. Conclusion: Higher diabetes-related distress was moderately associated with lower quality of life, whereas better self-care was moderately associated with higher quality of life among patients with type 2 diabetes mellitus. Because this study employed a cross-sectional design and unadjusted bivariate analysis, causal relationships and independent associations cannot be established.