Cytocompatible shape memory polymers activated by thermal or photothermal triggers have been developed and established as powerful "smart material" platforms for both basic and translational research. Shape memory polymers (SMPs) that could be triggered directly by biological activity have not, in contrast, been reported. The goal of this study was to develop an SMP that responds directly to enzymatic activity and can do so under isothermal cell culture conditions. To achieve this goal, we designed an SMP with a shape fixing component, poly(ε-caprolactone) (PCL), that is vulnerable to enzymatic degradation and a shape memory component, Pellethane, that is enzymatically stable - as the shape fixing component undergoes enzymatically-catalyzed degradation, the SMP returns to its original, programmed shape. We quantitatively and qualitatively analyzed material properties, shape memory performance, and cytocompatibility of the enzymatically-catalyzed shape memory response. The results demonstrate enzymatic recovery, as contraction of tensile specimens, using bulk enzymatic degradation experiments and show that shape recovery is achieved by degradation of the PCL shape-fixing phase. The results further showed that both the materials and the process of enzymatic shape recovery are cytocompatible. Thus, the SMP design reported here represents both an enzyme responsive material capable of applying a programmed shape change or direct mechanical force and an SMP that could respond directly to biological activity. STATEMENT OF SIGNIFICANCE: Cytocompatible shape memory polymers activated by thermal or photothermal triggers have become powerful "smart material" platforms for basic and translational research. Shape memory polymers that could be triggered directly by biological activity have not, in contrast, been reported. Here we report an enzymatically triggered shape memory polymer that changes its shape isothermally in response to enzymatic activity. We successfully demonstrate enzymatic recovery using bulk enzymatic degradation experiments and show that shape recovery is achieved by degradation of the shape-fixing phase. We further show that both the materials and the process of enzymatic shape recovery are cytocompatible. This new shape memory polymer design can be anticipated to enable new applications in basic and applied materials science as a stimulus responsive material.