The property and applications of bio-based solvents in place of petroleum-based ones for natural product extractions are discussed in this chapter including vegetable oils, terpenes, 2-methyltetrahydrofuran, bio-ethanol and natural deep eutectic solvents (NADES). Several commonly used prediction techniques such as Hansen solubility parameters (HSP), COnductor-like Screening MOdel for Real Solvents (COSMO-RS) and life-cycle assessment (LCA) are introduced to evaluate theoretical solubility and environmental impacts during all stages of a solvent’s life. Besides, the revisit of polar paradox theory helps us to better understand the solubilization mechanism underpinning the extraction. This chapter is intended to describe not only past and current achievements and challenges, but also to give visions for more sustainable applications in this increasingly important field of chemistry. Finally, it is also intended to draw the way to more rigorous research going beyond empiricism, which is still the usual approach in plant extractions.