This article aims to study the effects of material formulation and processing parameters on mechanical properties of bioepoxy/clay nanocomposites based on epoxidized soybean oil (ESO) via Taguchi design of experiments (DoEs). A mixed-level DoE with an L 16 orthogonal array was constructed to achieve maximum levels of tensile strength, tensile modulus, and impact strength for corresponding bionanocomposites. Pareto analysis of variance (ANOVA) was used to identify significant factors and preferred formulations in the manufacture of bioepoxy/clay nanocomposites. The ESO content was found to have the most significant effect with regards to bionanocomposite mechanical properties with contribution percentages of 66.63, 72.96, and 40.14% for their tensile strength, tensile modulus, and impact strength, respectively. With regards to material processing parameters, mechanical mixing speed was identified as a critical factor to achieve optimal tensile and impact properties. Nonetheless, the results also indicated clay content to be a significant factor for tensile strength, whereas curing agent type was vital for the improvement of tensile modulus and impact strength. Clay type and sonication time were also found to be significant factors for impact strength. In contrast to this, manufacturing parameters such as mechanical mixing temperature, mixing time, and sonication frequency were considered to be non-significant factors due to their low cumulative contribution percentages of <10%. Finally, experimental confirmation tests based on the preferred combination of factors demonstrated good agreement with statistically predicted results.