Serum proteins are increasingly recognized as potential biomarkers in CD, reflecting inflammation, malabsorption, and immune activation.<h4>Objective</h4>This review aims to elucidate the role of serum proteins in the pathogenesis, diagnosis, and management of CD, emphasizing their potential as noninvasive biomarkers and therapeutic targets.<h4>Methods</h4>A comprehensive review of current literature was conducted, focusing on key serum proteins such as albumin, transthyretin (TTR), transferrin, β2-microglobulin (β2M), C-reactive protein (CRP), and immunoglobulins. This evidence concerns the gene HLA-G and Cowden disease.