Recently, it has been discovered that neoagarohexaose (NA6) contained in neoagarooligosaccharides (NAO), which originate from the beta-agarase hydrolysis of agarose in red algae, has various medical effects. This has led to growing interest in establishing an industrial-utilizable process for high-purity separation of NA6 from NAO, which has, however, yet to be realized. To address this issue, we attempt to develop an efficient simulated-moving-bed (SMB) process for continuous-mode separation of NA6 from NAO with high purity and high yield, which was named "NA6-SMB" in this article. It was found first that the most suitable adsorbent for the targeted SMB separation was the ion-exclusion resin of sodium form with 4% crosslinkage, and its proper operating temperature was 60 degrees C. For the selected absorbent with the aforementioned properties, the intrinsic parameters of all NAO components were determined. Using the resultant parameter values, the configuration and operation parameters of the NA6-SMB were designed such that the high-purity separation of NA6 could be realized and kept stable throughout a long period of SMB operation while maximizing throughput. The separation efficiency of such designed NA6-SMB was first validated by model simulations, and then verified by experiments, which confirmed that the NA6 product of 98.7% purity could be obtained continuously throughout the long-term NA6-SMB processing while keeping its loss below 1%. Finally, an additional SMB was developed to treat the non-product stream of the NA6-SMB for the purpose of producing high-purity NA4 (>99%), which has been considered worthy of testing its medical efficacy and physiological activation in large quantity.