Frozen shoulder (FS) is a disease caused by an inflammatory condition that causes severe pain and decreased range of motion by loss of glenohumeral mobility. Frozen Shoulder restricts daily life's functional aspect, increasing morbidity. Hypertension and diabetes mellitus are risk factors that make an FS poor prognosis during treatment because of the diabetes glycation process and hypertension-enhanced vascularization. Prolotherapy injects an irritant solution into the tendon, joints, ligaments, and joint spaces to release growth factors and collagen deposition, reducing pain, restoring joint stability, and increasing the quality of life. We report 3 cases of patients with confirmed FS. Patient A with no comorbidity, patient B with diabetes mellitus, and patient C with hypertension, with all patient's chief complaints of shoulder pain and limited ROM, and symptoms affected the general quality of daily life. This patient was provided injection with Prolotherapy treatment combined with physical therapy intervention. Patient A had significantly improved ROM to maximum after 6 weeks with relieved pain and improved shoulder function. Patients B and C showed increased ROM, still tiny, decreased pain, and improved shoulder function. In conclusion, prolotherapy demonstrated a beneficial effect in a patient with FS with comorbidities, although not to the maximum extent in patients without comorbidity.