To evaluate the relationship between physical activity with co morbidities and health-related quality of life in type 2 diabetic patients with and without restless legs syndrome (RLS). This is an observational study, set at tertiary care diabetic outpatient clinic, where 200 consecutive type 2 diabetic patients and 47 controls participated. Physical activity level was established by the International Physical Activity Questionnaire (IPAQ) and RLS diagnosis and RLS severity were established using the criteria defined by the International Restless Legs Syndrome Study Group; excessive daytime sleepiness was evaluated by the Epworth Sleepiness Scale, quality of sleep by the Pittsburgh Sleep Quality Index and Health-Related Quality of Life by the Short-Form Health Survey (SF-36). Depressive symptoms were investigated by Beck Depression Inventory (BDI- II). Among all diabetic patients (58 % women, mean age 52.7 ± 5.7), disease duration varied from 1 to 30 years (11.7 ± 7.5). Diabetic patients had more hypertension (76 %), peripheral neuropathy (65 %), and depressive symptoms (31 %) than controls; no gender differences were found between cases with and without depressive symptoms. RLS patients (72 % female) had worse quality of sleep. With regards to the quality of life domains, more active RLS diabetic patients had better perception of functional capacity, physical limitation, pain, and general health state (p < 0.05). RLS symptom severity did not vary according to physical activity (IPAQ level). This study shows that the physical activity is associated with a better perception of functional capacity, physical limitation, and pain in diabetic patients with RLS; thus a more active lifestyle should be encouraged.