The concentrations of some heavy metals (Fe, Zn, Mn, Cu, Mo, Pb, Cd) were measured in river waters, macrozoobenthos, and fish (Kura scrapers) from one of the most developed mining areas in Armenia, the Debed River catchment basin. In order to assess heavy metal contamination and its hydro-ecological and health effects, the macrozoobenthos quantitative and qualitative parameters, geo-accumulation index, and hazard index were determined. Microalgal extraction experiments were conducted to assess the microalgal remediation efficiency for heavy metal removal from mining wastewaters. The results showed that the rivers in many sites were polluted with different heavy metals induced by mining activities, which adversely affected macrozoobenthos growth and caused human health risks in the case of waters used for drinking purposes. However, the river fish, particularly Kura scrapers, were determined to be safe for consumption by the local people, as per the conditions of the evaluated fish ingestion rate. The results have shown that microalgal remediation, particularly with Desmodesmus abundans M3456, can be used for the efficient removal ~(62–100%) of certain emerging contaminants (Mn, Pb, Cu, Zn, Cd) from mining wastewater discharged in the Debed catchment basin.