This work reports the continuous isomerization of glucose to fructose in aqueous media under mild conditions using a mixed oxide hydrotalcite‐derived catalyst based on Ca and Al. Different operational parameters of the continuous flow fix‐bed catalytic reactor system were studied. At the optimal conditions, the Ca−Al‐based catalyst achieved a very high conversion and almost quantitative selectivity towards fructose, this being one of the few successful examples of a heterogeneous catalyst capable of carrying out this reaction in a continuous process. Importantly, catalytic activity held steady during four hours on stream, and slight deactivation occurring could be practically overcome by thermal regeneration of the catalyst. [ABSTRACT FROM AUTHOR]