Bio-based organic acids constitute an important group of building block chemicals that can be produced from renewable resources, becoming a sustainable alternative to conventional petrochemical-derived commodities. However, due to the growing number of green solvents emerging as extraction media, the proper solvent selection for biomolecule separation from fermentation broths has become a key challenge in the bio-refinery industry. The overall aim of this work is to develop a roadmap to select and design green solvents for sustainable downstream processing of bio-based organic acids. To this end, a wide range of neoteric solvents (ionic liquids, eutectic solvents and bio-based solvents) were systematically evaluated for the recovery of relevant bio-organic acids through combination of experimental and COSMO-RS molecular simulation methods. Comprehensive thermodynamic analyses evaluating the organic acid partition coefficients, excess enthalpy contributions, solvent-water affinity, and process spontaneity were performed to elucidate the main mechanism driving the separation process and to provide essential guidelines for further solvent development. Based on these findings, a rational screening approach was established to identify suitable solvents for the recovery of structurally different bio-organic acids. Ultimately, this paper provides a green solvent selection guide to design sustainable separation processes of bio-based organic acids, as valuable platform chemicals transitioning towards a bio-based economy.