Nano polystyrene (PS) particles and antibiotics universally co-exist, posing a threat to crop plants and hence human health, nevertheless, there is limited research on their combined toxic effects along with major influential factors, especially root exudates, on crop plants. This study aimed to investigate the response of Chrysanthemum coronarium L. to the co-pollution of nanoplastics and tetracycline (TC), as well as the effect of root exudates on this response. Based on a hydroponic experiment, the biochemical and physiological indices of Chrysanthemum coronarium L. were measured after 7 days of exposure. Results revealed that the co-pollution of TC and PS caused significant oxidative damage to the plants, resulting in reduced biomass. Amongst the two contaminants, TC played a more prominent role. PS could enter the root tissue, and the uptake of TC and PS by plant roots was synergetic. Malic acid, oxalic acid, and formic acid could explain 65.1% of the variation in biochemical parameters and biomass of the roots. These compounds affected the photosynthesis and biomass of Chrysanthemum coronarium L. by gradually lowering root reactive oxygen species (ROS) and leaf ROS. In contrast, the impact of rhizobacteria on the toxic response of the plants was relatively minor. These findings suggested that root exudates could alleviate the toxic response of plants to the co-pollution of TC and PS. This study enhances our understanding of the role of root exudates, providing insights for agricultural management and ensuring food safety.