Antibiotics can be accidentally introduced into farmland by wastewater irrigation, and the environmental effects are still unclear. In this study, the effects of oxytetracycline on the residue of imidacloprid in soil and radishes were investigated. Besides, the rhizosphere microbiome and radish metabolome were analyzed. It showed that the persistence of imidacloprid in soil was unchanged, but the content of olefin-imidacloprid was increased by oxytetracycline. The residue of imidacloprid in radishes was increased by nearly 1.5 times, and the hazard index of imidacloprid was significantly raised by 1.5−4 times. Oxytetracycline remodeled the rhizosphere microbiome, including Actinobe, Elusimic, and Firmicutes, and influenced the metabolome of radishes. Especially, some amino acid metabolic pathways in radish were downregulated, which might be involved in imidacloprid degradation. It can be assumed that oxytetracycline increased the imidacloprid residue in radish through disturbing the plantrhizosphere microbiome holobiont and, thus, increased the pesticide dietary risk.