Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is now widely used in the treatment of diabetes and obesity. However, there are still insufficient safety data for the use of GLP-1RAs in oncological and hemato-oncological patients, as they have not been included in clinical trials. The potential prooncogenic activity of GLP-1RAs in patients with thyroid cancer has been reported, raising concerns about the safety of semaglutide in oncological and hemato-oncological patients. We present a case of a 57-year-old man, who suffered from class III obesity (BMI: 40.4 kg/m²), type 2 diabetes, and chronic lymphocytic leukemia (CLL; RAI stage I and Binet A stage). The patient started therapy with semaglutide to manage obesity and diabetes; he had already begun systemic therapy for CLL with obinutuzumab and venetoclax, which was continued after its complete remission. More than 3 years of semaglutide therapy improved the patients’ metabolic control of diabetes and resulted in significant weight loss (16% of the initial body mass), with no reported adverse drug reactions and without compromising hematologic stability. Our case report suggests that hemato-oncological patients should not be categorically excluded from treatment with semaglutide, as long as close hematological and clinical monitoring is ensured. However, as this observation is based on a single case report, no definitive general recommendations regarding the safety of semaglutide in hemato-oncological patients can be made at this time.