Abstract: The powder spreading process is one of the key processes in the powder-bed-based additive manufacturing (AM) technology. The roller-spreading parameters include the powder spreading layer thickness H, roller’s diameter D, roller’s rotational speed ω and translational velocity V, which have a major impact on the powder spreadability in AM processes. In this paper, the nylon powder was taken as the research object, and the discrete element method (DEM) was deployed to simulate the nylon powder spreading process by a roller. The three powder spreadability indicators including the deposition fraction, percent coverage and deposition rate were established. The central composite design (CCD) model was used to generate 30 groups of simulation cases. The regression models of three powder spreadability indicators were fitted by the response surface method (RSM). The analysis of variance was used to prove the accuracy and predicting effectiveness of regression models. In addition, the effect of process parameters on powder spreadability indicators was analyzed in detail. The results showed that the powder spreading layer thickness H was a leading influencing factor. The roller’s translational velocity V was a less important influencing factor. The roller’s diameter D and rotational speed ω had a slight influence on powder spreadability indicators. Both the H and D with V were determined as the main interactive factors on powder spreadability indicators. The three powder spreadability indicators were taken as the optimization goal, and the multi-objective optimization of roller-spreading parameters was carried out by the expectation method. The predicted optimal combination of powder spreading parameters and powder spreadability indicators were obtained. Moreover, the optimal results were verified through the experiments. The results showed that the predicted results of powder spreadability indicators were in good agreement with experimental results. The research results in this paper can provide guidance for the optimization of roller-spreading parameters in AM.