Antibiotics are used to control certain bacterial diseases in plant agriculture. Understanding antibiotic uptake by edible vegetables after application and associated risks on plant microbiome and human health is critical. In this study, oxytetracycline and streptomycin, the two most commonly used antibiotics in plant agriculture, were applied to cherry radish via continuous soil drenching to study their translocations into plant tissues, influence on radish microbiome, and the potential health risk to mice. The results demonstrated that oxytetracycline induced hormesis in radish plants and both antibiotics were translocated into the leaves, fruits, and roots of radishes from the soil, with significantly higher plant uptake of streptomycin than oxytetracycline. Interestingly, the proportion of culturable oxytetracycline or streptomycin-resistant bacteria in the antibiotic-accumulated radish tissues was significantly higher than that in the antibiotic-free radish tissues, although both bacterial and fungal communities in different radish tissues were not affected by the accumulated antibiotics, demonstrating that antibiotic application could enrich antibiotic resistance in the plant microbiome. Feeding mice with antibiotics-accumulated radish tissues did not show significant effects on the weight and blood glucose levels of mice. Overall, this study provides important insights into the risk of using antibiotics in plant agriculture.