New opportunities in design surface with scientific advances: however, the rapid pace of scientific discoveries combined with the complexity of technical barriers often impedes new product development. Bio-based technologies, for instance, typically require decisions across complex multiscale system organizations that are difficult for humans to understand and formalize computationally. This paper addresses such challenges in science and design by weaving phases of empirical discovery, analytical description, and technological development in an integrative “D3 Methodology.” The phases are bridged with human-guided computational processes suitable for human-in-the-loop design approaches. Optimization of biolibraries, which are sets of standardized biological parts for adaptation into new products, is used as a characteristic design problem for demonstrating the methodology. Results from this test case suggest that biolibraries with synthetic biological components can promote the development of high-performance bio-based products. These new products motivate further scientific studies to characterize designed synthetic biological components, thus illustrating reciprocity among science and design. Successes in implementing each phase suggest the D3 Methodology is a feasible route for bio-based research and development and for driving the scientific inquiries of today toward the novel technologies of tomorrow.