Significance While mucosal folding is a ubiquitous phenomenon observed in many hollow or tubular human tissues/organs, recapitulating the process for tissue engineering has yet to be achieved. Here we fold a cell-laden hydrogel film to recapitulate the folding of a physiologically mimicking artificial mucosa. We attach the cell-laden hydrogel film onto a prestretched tough-hydrogel substrate, which after relaxation induces controlled patterns in the artificial mucosa. A combination of theory and numerical simulations predicts the folding conditions and the morphologies, thereby guiding the design of surface folding. This simple strategy can facilitate the understanding and engineering of mucosa for tissues/organs such as stomach, colon, and intestine. The work also demonstrates a paradigm in tissue engineering via harnessing mechanical instabilities guided by quantitative mechanics models.