Sjögren's syndrome is a chronic autoimmune disorder with limited therapeutic options. Glucagon-like peptide-1 (GLP-1) receptor agonists, primarily used for diabetes and obesity, have emerging evidence of anti-inflammatory and immunomodulatory effects. We present a case of a 37-year-old woman with primary Sjögren's syndrome and comorbid Hashimoto's thyroiditis and seronegative rheumatoid arthritis, who experienced frequent debilitating flares affecting her quality of life. After starting semaglutide for weight management and losing over 100 lbs, the patient reported a dramatic reduction in flare frequency and duration, with episodes decreasing from multi-week flares to approximately a single day. This case suggests that semaglutide may offer dual benefits in Sjögren's syndrome by combining substantial weight reduction with possible direct immunomodulatory effects. Further research is warranted to explore GLP-1 agonists as adjunctive therapy in the management of autoimmune diseases.