[Display omitted] • Depressant plays an important role in the reverse flotation separation of iron ores. • Biodegradable reagents can be effectively used as depressants in reverse hematite flotation. • Polysaccharides and polyphenolics are promising green depressants for hematite. • H-bonding is the most common adsorption mechanism between iron and green depressants. Due to environmental issues and the restrictions imposed on mineral flotation separation, the use of biodegradable and environmentally friendly reagents has gained widespread international attention. So far, several investigations have been conducted regarding the eco-friendly flotation separation of iron oxide ores for moving toward sustainable development and cleaner production. Yet, no critical review is specified on the green and eco-friendly depression reagents through their reverse flotation beneficiation. Therefore, this study will comprehensively discuss the previously conducted works in this area and provides suggestions for future assessments and developments. This robust study explored various adsorption aspects of natural-based depressants (polysaccharide-, polyphenolic-, and lignosulfonate-based) on iron oxide minerals (mainly hematite) to create a possible universal trend for each biodegradable depressant derivative. The laboratory and industrial experiments indicated that these depressants (except lignosulfonate-based) could selectively depress hematite at alkaline pHs and enhance its reverse flotation separation from their gangue phases (especially silicates as the main gangue phases). Although these eco-friendly depressants showed promising metallurgical results, several gaps still need to be addressed, notably in surface analyses and their adsorption mechanisms. [ABSTRACT FROM AUTHOR]