Heavy metals in coastal ecosystems caused by the increased expansion of urbanization, industrialization, and agricultural practices have become a significant environmental risk to human well-being. This study evaluates and compares 17 sediment quality indices to examine the possible ecological and human health risks associated with heavy metal concentrations in the sediments of the Nador lagoon in Morocco. The concentration order of the HMs and sulfurs evaluated was S > Sr > Ba > V > Zr > Zn > Cr > Rb > La > Cu > Pb > Ni > Ce > Nd > Co > Sc > Nb > Ga > Th > Y > Hf. Sulfurs, Pb, Sr, and Nd exhibited concentrations that exceeded geochemical background values. The analysis of the sediment quality indices allowed us to understand that the Nador lagoon was moderately to strongly polluted by heavy metals originating from various anthropogenic activities. Results from the Sediment Quality Guidelines indicated a toxic response in the benthic organisms within the lagoon, while the ecological hazard analysis revealed a very high risk of heavy metal contamination in the ecosystem. The Hazard Index for non-carcinogenic values was below the limit, suggesting a lack of non-cancerous effects. However, Cu and Pb concentrations surpassed the Lifetime Cancer Risk range, indicating a potential cancer risk with prolonged exposure. Integrating our research into coastal management frameworks can contribute to the preservation and enhancement of these coastal ecosystems for future generations.