The aim of the study is to assess QoL depending on the choice of therapeutic regimen. From a total of 200 patients, half (n = 100) were treated with insulin (66% were females, age 52.1 ± 7.4—group A), the remaining 100 received oral treatment (74% females, age 63.3 ± 8.3—group B). For self-assessment of QoL, the WHOQOL-BREF questionnaire was used. In group A, we found a negative influence of increased level of glycemia and occurrence of coexisting diseases in the somatic domain . In the psychological domain, frequent checkups showed a positive influence while circulatory failure produced negative results. For social domain, disobeying of recommended diet was strongly negative as well as increased levels of glycemia and coexisting disease for environmental domain. In group B, for somatic domain, correct values of glycemia and place of residence had positive influence. Incorrect values of BMI, WHR, and co-existing disease influenced the same domain negatively. In the psychological domain, a positive influence had place of residence but a negative BMI, ischemic heart disease, clinical complications. For environmental domain, a positive influence had correct values of glycemia but a negative BMI, ischemic heart disease and clinical complications. Finally, the social domain for group B was negatively influenced by BMI, ischemic heart disease, clinical complications, and lack of regular supervisions of glycemia level. A higher assessment of quality of life was found in the group of patients treated with oral hypoglycemic medicines in somatic and environmental domains, and in the group of patients treated with insulin in psychological domain.