Transthyretin is a homotetrameric thyroid-hormone-transporting protein that binds to the retinol binding protein thus being involved in metabolism, growth, fertility, homeostasis of the cardiovascular and central nervous system, cell differentiation, reproduction, development and maintenance the cognitive processes during aging. Currently, there are several methodologies for natively purifying TTR from plasma, serum, tears, and amyloid fibrils; however, these procedures are laborious. Herein, a low-cost and simple protocol to purify TTR from human plasma is described. It involves the separation of plasma proteins by size exclusion and DEAE chromatography. The homogeneity was assessed by SDS-PAGE and by tandem mass spectrometry using an Orbitrap-XL (Thermo, San Jose-CA).