Microplastic-derived dissolved organic matter (MP-DOM) is ubiquitous in water environment and exhibits photosensitivity. However, little is known about the effects of MP-DOM on the photodegradation of organic micropollutants in natural water. In this study, we investigated the effect of MP-DOM derived from two typical plastics, i.e., polystyrene (PS), and polyethylene (PE), on the photodegradation of a typical organic micropollutants sulfamethoxazole (SMX) in a simulative natural water system. MP-DOM exerted a significant inhibition on the SMX photodegradation, mainly attributed to the direct photolysis inhibition of SMX caused by the inner filter effect and the complexation effect. Despite the enhanced reactive oxygen species (ROS) generation with the increase of their steady-state concentration by 41.1 − 160.7 %, PS-DOM exhibited high oxidation resistance, causing an inhibition on the photodegradation of SMX probably through transferring electrons to the SMX intermediates. This study helps to deepen the understanding of microplastic photochemical behavior in natural water.