Abstract
Medicago sativa L. (alfalfa) is increasingly recognized as a rich source of health-promoting phytochemicals whose efficient, sustainable recovery remains technically challenging. This systematic review revises current extraction strategies and associated bioactive profiles, providing an evidence-based roadmap to obtain extracts valuable for the food, nutraceutical and pharmaceutical sectors. A PRISMA-guided search of PubMed, Scopus and Web of Science (literature up to March 2025) yielded 80 eligible studies. These investigations collectively report 124 distinct bioactive constituents—classified into 13 chemotypes (alkaloids, amino-acid derivatives, carbohydrates, carotenoids, coumarins, coumestans, flavonoids, phenolics, pigments, saponins, sterols, terpenoids and vitamins)—isolated from alfalfa leaves, stems, roots or seeds. Extraction technologies were grouped as conventional (maceration, Soxhlet, hydrodistillation) or innovative (ultrasound-, microwave-, enzyme-, pulsed-electric-field and supercritical-fluid-assisted methods). Meta-comparison shows that innovative technologies—particularly ultrasound-assisted extraction, supercritical CO₂ (with ethanol as co-solvent) achieves equal or superior yields of key flavonoids, phenolics and triterpene saponins while reducing solvent consumption (30–90 %), energy use (40–70 %) and thermal degradation relative to conventional techniques.