Periostin, a component of the extracellular matrix expressed by fibroblasts in normal tissues and stroma of primary tumor, is associated with asthma and metastatic colony formation. It consists of four fasciclin (FAS1) domains, an extracellular cell adhesion domain, and a cysteine-rich EMILIN (EMI) domain involved in protein-protein interactions. Here we present synthesis of EMI and FAS1 domains of human Periostin and structural characteristics of each domain using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. EMI domain of human Periostin contains six cysteines with three intramolecular disulfide bonds. We have successfully refolded EMI domain using redox buffer condition. We used E. coli expression system for the expression of all FAS1 domains of human Periostin. FAS1-I and III domains were in insoluble faction after lysis. However FAS1-II and IV were in soluble fraction, we therefore focused on FAS1-II and IV for further studies. Circular dichroism studies clearly showed that FAS1-II and IV domains are composed of mixture of -helix and -sheet with flexible loop, which is consistent with a previously determined FAS1 domain from Drosophila melanogaster. These results suggest that human Periostin domains especially FAS1-II and IV are good targets for further biochemical and structural studies.