This study aimed to assess Oral Health-Related Quality of Life (OHQoL) and satisfaction in patients who had complete denture treatment and were diagnosed with systemic diseases. Eighty edentulous patients using new complete dentures were separated into four groups according to their diseases [diabetes mellitus (DM)/osteoporosis (OP)/hypertension (HP)/healthy (control)]. The groups answered the Turkish version of the United Kingdom-Oral Health-Related Quality of Life (OHQoL-UK) and Visual Analog Scale (VAS) questionnaire four weeks after treatment. OHQoL-UK scores were slightly higher for females regardless of the type of disease. Compared with the control participants (57.95±5.33), the scores of the OHQoL-UK were not significantly different in OP and HP groups except for the DM group (58.7±5.37, 58.9±6.44, 45.3±5.19 respectively). DM was significantly associated with the increase of OHQoL values (p<0.05). Patients in all groups reported significantly higher “physical health” scores than other subdomains of OHQoL-UK, although positive correlations were determined among them. Presence of disease had no relationship to the VAS scores. This study shows that systemic diseases might not affect and predict patients' satisfaction with their complete dentures and OHQoL. DM is an independent risk factor for oral health. Satisfaction with the prosthesis might concern a patient's level of OHQoL.