Aquatic environments are progressively impacted by the presence of contaminants of emerging concern (CECs). However, the determination of their concentrations in marine sediments remains challenging due to the complexity of this matrix and the reliance on hazardous organic solvents for conventional extractions. In this study, natural deep eutectic solvents (NADES) were explored as greener alternatives for the extraction of CECs from marine sediments. Three formulations, choline chloride:glycerol (1:2) (ChCl:Gly), choline chloride:urea:water (1:2:10) (ChCl:U:W), and betaine:urea:water (1:1:10) (B:U:W), prepared at mole/mole ratios, were evaluated using both in-house sediment reference materials (SRMs) and environmental samples from the Red Sea. Matrix-matched calibration ensured reliable quantification, with all analytes showing excellent linearity. ChCl:U:W showed the best overall performance, achieving high recoveries across multiple contaminant classes (antibiotics, antiprotozoals, beta-agonists, herbicides, and analgesics) while remaining instrument-friendly. B:U:W showed moderate performance for SRMs but excelled in environmental samples, extracting the widest range of analytes and higher concentrations of several CECs compared to the conventional method. Overall, NADES outperformed the conventional method in both recovery efficiency and eco-friendliness. This was further supported by the AGREE evaluation, where NADES scored 0.67 compared to 0.28 for the conventional method, confirming their superior greenness. These results highlight the potential of NADES, particularly ChCl:U:W and B:U:W, as sustainable and cost-effective alternatives for monitoring CECs in marine sediments over time.