Sheeza Rasheed, Xiaoai Wang, Urwah Shafeeq, Jingyu Wei, Chenchen Yao, Yeboah Asuama Kwasi, Mufzala, Yuqing Duan, Kai Hu, Meihong Cai, Wenlin Li, Haihui Zhang
Conventional lipid extraction methods face three critical limitations: reliance on toxic organic solvents (hexane/chloroform), inability to process wet biomass without energy-intensive drying, and thermal degradation of omega-3 polyunsaturated fatty acids. This review critically assesses Subcritical fluid technology (SFT) as a sustainable alternative. SFT utilizes non-toxic solvents (water, ethanol, dimethyl ether) at moderate temperatures (100–250°C) and pressures (10–100 bar) below critical points, offering tunable polarity (ε = 80→25), gas-like diffusivities, and direct wet biomass processing. These properties enable selective lipid extraction with yields exceeding 90%, preservation of thermolabile bioactives (EPA/DHA retention >90%), and elimination of toxic residues. SFT demonstrates superior environmental, economic (energy savings 20–40%), and quality outcomes across microalgae, marine by-products, and oilseeds. This review provides a comprehensive framework, positioning SFT as a potential cornerstone for sustainable high-value lipid production across food, nutraceutical, and pharmaceutical industries, while identifying future research priorities in scalability and circular bioeconomy integration.