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In this paper, a differential neural network (DNN) implemented as a robust observer estimates the dynamics of perturbed uncertain nonlinear systems affected by exogenous unknown inputs. In the first stage, the identification error converges into a neighborhood around the origin. Then, the second-order sliding mode supertwisting algorithm implemented as a robust exact differentiator reconstructed the unknown inputs. The approach proposed in this paper can be applied in the case of full access to the state vector (identification problem) and in the case of partial access to the state vector (estimation problem). In the second case, the nonlinear system under study must have well-defined full relative degree with respect to the unknown input. Numerical examples showed the effectiveness of the proposed algorithm. The first example tested the DNN working as an identifier into a mathematical model describing the dynamics of a spatial minisatellite. The second example (with a DNN implemented as an observer) tested the methodology of this paper over a single link flexible robot manipulator represented in a canonical (Brunovsky) form. In both examples, the mathematical models served as data generators in the testing of the neural networks. Even when not exact mathematical description of both models was used in the input estimation, the accuracy obtained with the DNN is comparable with the case of applying a high-order differentiator with complete knowledge of the plant. [ABSTRACT FROM AUTHOR]