To address the issue that dyes are recalcitrant to hydrolysis and conventional water treatment strategies, an ultraviolet light-emitting diode (UV-LED)/periodate (PI) advanced oxidation process was developed for dye removal. The results showed that this system was applicable to a wide pH range. The dyes were completely removed in 40 minutes optimally with 270 nm UV-LED and 1 mmol/L PI. NO3- and HCO3- showed inhibitory effects on dye decomposition, while Cl-, SO2-4 and humic acid had a negligible effect on the system. Quenching experiments and electron paramagnetic resonance experiments were conducted to explore the reactive species involved in the oxidation process. It was confirmed that hydroxyl radicals and singlet oxygen dominated the degradation of pollutants. In addition, the transformation products of methylene blue (MB) in the system were explored and the potential reaction pathway was proposed. Furthermore, the toxicity of MB and the transformation products were predicted via a series of in silico QSAR-based prediction approaches. It was found that the biodegradability of the transformed products was significantly improved. However, some products still exhibited acute/chronic toxicity.