Mineral trioxide aggregate (MTA) can provide bioactivity to poly‐caprolactone (PCL), which is an inert polymer used to print scaffolds. However, testing all combinations of scaffold characteristics (e.g., composition, pore size, and distribution) to optimize properties of scaffolds is time‐consuming and costly. The Taguchi's methods can identify characteristics that have major influences on the properties of complex designs, hence decreasing the number of combinations to be tested. The objective was to assess the potential of Taguchi's methods as a predictive tool for the optimization of bioactive scaffold printed using electro‐hydro dynamic jetting. A three‐level approach assessed the influence of PCL/MTA proportion, pore size, fiber dimension and number of layers in pH, degradation rate, porosity, yield strength, and Young's modulus. Data were analyzed using Tukey's honest significant difference test, analysis of mean and signal‐to‐noise ratio (S/N) test. Cytocompatibility and differentiation potential were assessed for 5 and 30 days using dental pulp stem cells and analyzed with one‐way analysis of variance (proliferation) or Mann–Whitney (qPCR). The S/N ratio and analysis of mean showed that fiber diameter and composition were the most influential characteristics in all properties. The experimental data confirmed that the addition of MTA to PCL increased the pH and scaffold degradation. Only PCL and PCL with 4% MTA allowed cell proliferation. The latter increased the genetic expression of ALP, COL‐1, OCN, and MSX‐1. The theoretical predictions were confirmed by the experiments. The Taguchi's identified the inputs that can be disregarded to optimize 3D printed meshed bioactive scaffolds.