The reduction and dehydration treatment of contaminated sediment from rivers and lakes is a prerequisite for ensuring the subsequent safe disposal. In this study, micro-nano bubbles (MBs) technology was creatively proposed for the conditioning treatment of contaminated sediment to improve its sedimentation and dehydration performance. Orthogonal experiment and single factor experiment were conducted to optimize factors such as bubble size, intake air volume and treatment time. The conditioning effect was analyzed through direct and indirect characterization parameters. The results showed that the range (R) values for bubble size, intake air volume and treatment time were 101.8, 94.5 and 51.6 respectively in the orthogonal analysis. The optimum bubble size, intake air volume and treatment time were 1 μm, 30 L/min and 90 s. At this time, the CST of conditioned sediment decreased to 160.6 s (the reduction rate of 89.29%) and the moisture content of the filter cake decreased to 65.2%. Through the analysis of polysaccharide and MLSS, it was found that the MBs effectively exerted the oxidation and extracellular polymer cracking properties, which released polysaccharides that easily bind to water. The SEM analysis of the filter cake showed a loose structure and rich porosity compared to the undisturbed sediment. Meanwhile, the MBs promoted the homogenization degree of conditioners to achieve efficient dehydration. Therefore, MBs conditioning was verified as a novel and promising technique for improving the dehydration performance of river and lake contaminated sediment.