Abstract: Sulfamethoxazole (SMX) is a broad-spectrum sulfonamide antibiotic widely used due to its extensive antimicrobial spectrum and strong chemical stability. However, its large-scale production and use have caused a variety of environmental and public health concerns. In terms of environmental occurrence, SMX has been detected in water bodies, soil, sediments, and other environmental media. Its concentrations in special water environments such as hospital wastewater and livestock breeding wastewater are considerably higher than those in conventional water bodies. Specifically, the SMX concentration in raw wastewater from a South African hospital is up to 34.57 μg·L^-1, and that in livestock farm wastewater reaches 63.6 μg·L^-1. The concentration of SMX in soil falls within the range from μg·kg^-1 to mg·kg^-1, with a peak value of 690 μg·kg^-1 in heavily contaminated soil from organic vegetable planting bases. As an indicator of long-term cumulative pollution, sediments contain SMX at concentrations ranging from 2.88 to 4 125 μg·kg^-1, with prominent accumulation in pollution hotspots downstream of wastewater treatment plants. SMX exposure imposes potential toxic hazards on terrestrial organisms (e.g., earthworms), aquatic organisms (e.g., fish and shellfish), as well as human beings. It alters the structural composition of soil microbial communities and disturbs the intestinal microbiota of earthworms. For aquatic organisms, SMX can induce neurotoxicity, oxidative stress, immunosuppression and metabolic disorders, and facilitate the horizontal spread of antibiotic resistance genes including sul1, sul2 and sul3. Humans are exposed to SMX through multiple pathways, including drinking water, vegetables, and aquatic products. Long-term intake may increase the risk of diseases such as kidney stones and premature ovarian failure. Significant accumulation has also been detected in the urine of high-risk groups like children and pregnant women. Different species exhibit varied toxicological responses to SMX: aquatic organisms are more sensitive to neurotoxicity and metabolic disturbances, while terrestrial organisms are more susceptible to gut microbial disruptions. Future research should focus on the environmental fate of SMX transformation products, the combined toxic effects in multi-pollutant systems, and enhancing public awareness and policy development to better address the environmental and health challenges posed by SMX.