AbstractThis work reported the application of a twin‐column recycling chromatography system for the separation of three minor impurities in crude aloe‐emodin. The whole process went through three steps, each using a different mobile phase to separate corresponding impurity, which were integrated and automatically operated in a single device. Despite these impurities peaked closely in high‐performance liquid chromatography, they were successfully purified to a content exceeding 97%. In addition, the lab‐scale separation could reach the yields at the mg‐level. The high efficacy should be mainly attributed to the introduction of a small step solvent gradient between the upstream and downstream columns, which helped to counterbalance the band broadening. This report suggested that such an automated chromatographic system could provide fast and accurate separation of multiple impurities, allow the process of high‐throughput samples, and reduce the time required for purification and recovery of minor impurities in drugs.