Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterized by diverse clinical manifestations. While xerophthalmia and xerostomia are hallmark symptoms, the disease often involves multiple organ systems, including the kidneys, lungs, nervous system, and gastrointestinal tract, leading to systemic morbidity in severe cases. Despite extensive research, the precise pathogenesis of pSS remains unclear, likely involving infectious, hormonal, and genetic factors. Emerging evidence highlights the microbiome as a key contributor to autoimmune diseases, including pSS. Dysbiosis in the oral, ocular, gut, and genital microbiomes plays a critical role in disease onset, progression, and variability. This review summarizes current findings on microbiome alterations in pSS, emphasizing their role in pathogenesis and clinical features, and explores microbiome-targeted therapies. Understanding the role of the microbiome in pSS pathophysiology could advance disease management and inspire targeted therapeutic strategies.