Abstract We proposed a multilayered spatial optical differentiator designing method by use of the deep neural network (DNN). After trained for approximately 30 h, the DNN is able to predict the reflection coefficient of a 12-layer multilayer film with high fidelity (validation mean squared error × 10−4). As a useful example, a second-order spatial optical differentiator was then designed. Compared with the general optimization method, the machine learning could help to quickly generate a wavefront computing device at an about 6-times faster speed. The performance of the designed device is confirmed from the comparison with the theoretical ideal operation output. Another first-order spatial optical differentiator was also designed to validate the generality of the method. The results indicate that the DNN may have a bright future in designing devices capable of all kinds of complex time-space wavefront mathematical operation, in particular based on the multilayer material systems.