Reducible sodium alginate nanospheres cross-linked with disulfide linkages were developed for site-specific drug delivery in inflammatory bowel disease. The nanospheres were synthesized by self-assembly of amphiphilic thiolated sodium alginate (TSA) in deionized water and subsequently producing disulfide bond cross-linking. TEM showed that the nanospheres had a spherical core–shell configuration with a size of about 170nm. Dynamic light scattering showed that the nanospheres had high stability, narrow size distribution and a pH-dependent swelling transition. Cytotoxicity study indicated that the nanospheres had no apparent cell inhibition. Moreover, the size of the nanospheres increased because of the cleavage of disulfides within their network structures in 10mM glutathione (GSH) solution. As compared with that in GSH-free buffer, the drug release in pH 6.0 buffer with GSH from drug-loaded nanospheres exhibited a marked increase, indicating that the nanospheres may be used for colon-specific drug delivery.