Bio-based concrete, which utilizes recycled agricultural waste as aggregates, has emerged as a sustainable alternative material in the construction industry. Optimizing its combined mechanical and thermal performance can promote its environmental and energy benefits. To achieve this, this paper presents a multi-objective optimization approach to improve the overall performance of bio-based concrete based on multiscale structural features, considering the porosity, shape, orientation, and volume fraction. Optimization strategies are provided for three main industrial applications. Furthermore, this study addresses multiple design requirements, including high-volume bio-aggregates, more demanding performance requirements, low densities, and humid environments. The optimization results demonstrate that the optimal solution varies with industrial applications and requirements. Consequently, we quantitatively provide specific optimal solutions for each case, and offer designers three preferences for mechanical properties, insulation, or balanced performance. Overall, this study optimizes the comprehensive performance of bio-based concrete in terms of multiscale structures, thereby contributing to a more sustainable construction industry.