In this study, pragmatic prospection of multi-walled carbon nanotubes (MWCNTs) is conducted considering their impacts on Cd transformation, microbial activity and natural organic matter (NOM) in sediments. Indeed, dose-dependent of MWCNTs acceleration in Cd sedimentation and immobilization in water-sediment interface has been found. Unexpectedly, even with the reduced Cd bioavailability, high ratios of MWCNTs incorporation led to exacerbated microbial inactivation. Besides, we noted that MWCNTs significantly lowered NOM contents in sediments. Chemical characterization results also demonstrated that high ratios of MWCNTs incorporation reduced the aromaticity, hydrophobicity and humification of fulvic acid (FA) and humic acid (HA) in sediments. The Cd binding results confirmed that quantity and chemical variation of NOM affected their central ability to Cd binding, referring to significant decrease in combined Cd contents. The findings indicated that reduction in humic substances and chemical structure variation might be the important reason attributed to the MWCNTs toxicity. This study provides novel mechanisms understanding the fate of carbon nanotubes considering the balance in environmental benefit and potential risks.