The majority of contemporary chemical processes rely on non-renewable resources and reagents associated with negative impact on environment and human health. For this reason, the Safe-and-Sustainable-by-Design (SSbD) framework was launched by the European Commission to guide the innovation process towards green and safe chemical products. In this work, we demonstrate how SSbD guided a multidisciplinary study for facile identification of non-toxic bisphenol A (BPA) analogues suitable for incorporation into high-performance polymeric materials. Toxicological evaluation of a library of bisphenols with an in silico model identified promising candidates that were synthesized from renewable lignin-sourced feedstocks using benign catalytic routes. Subsequently, in vitro evaluation identified an optimal BPA analogue, that was successfully incorporated into a polyester with attractive properties for future consumer products. As such, the work showcases how the combination of synthetic chemistry, toxicology, and computational modelling enables an effective workflow towards renewable and inherently safe chemicals.