© 2020 Elsevier B.V. In this study, highly crystalline, mesoporous, small sized, stable, and efficient nitrogen-doped (N-doped) Ceria nanoparticles were synthesized using deep eutectic solvent (DES) and used for the photocatalytic degradation of sulfamethaxazole (SMX), a widely used human medication and emerging water contaminant. The N-doped Ceria resulted in 96% removal of SMX versus 59% by Ceria under solar irradiation at 150 min time using [SMX]0 = 10 mg/L and [Ceria]0 = [N-doped Ceria]0 = 0.5 g/L. The solar irradiation of the photocatalysts produced [rad]OH which was proved with electron spin resonance (ESR) spectroscopy and radical scavenger studies and the resulting [rad]OH caused the degradation of SMX. The [rad]OH showed high second-order rate constant with SMX, e.g., 4.9 × 109 M−1 s−1. The photocatalytic degradation of SMX was influenced by pH, concentrations of SMX and photocatalysts, inorganic anions, and natural organic matter. The kinetics of the photocatalytic degradation of SMX was found to be pseudo-first-order. The SMX degradation resulted into several products which were identified by UPLC-MS/MS and the resulting products were used to establish degradation pathways of SMX. The synthesized Ceria and N-doped Ceria also showed good antimicrobial activities towards Staphylococcus aureus and Escherichia coli. The treatment of SMX showed high reusability of N-doped Ceria, low leaching of cerium ions into reaction solution, and high decline in toxicity of SMX which suggests high potential of the synthesized nanoparticles towards SMX degradation.