The zebrafish (Danio rerio) has become an indispensable model in toxicological research, bridging environmental monitoring, disease modeling, and preclinical drug screening. This study presents a comprehensive bibliometric and methodological analysis of 20,291 publications from 2014 to 2024, revealing distinct trends and opportunities in the field. Acute toxicity studies dominate the literature (39.36%), followed by neurotoxicity (19.50%) and immunotoxicity (11.39%), reflecting the widespread adoption of high-throughput embryonic assays such as the Fish Embryo Acute Toxicity (FET) test. While the model’s strengths in rapid hazard assessment are well-established, our analysis identifies a significant emphasis on early developmental stages (embryos and larvae), creating a critical gap in chronic toxicity evaluation and adult organism studies. Methodologically, zebrafish toxicology leverages a versatile toolkit including behavioral phenotyping, high-resolution imaging, molecular analyses, and omics technologies. However, applications often remain isolated within specific domains, highlighting the need for more integrative approaches. The field is characterized by strong growth led by China and the United States, with research published predominantly in environmental and multidisciplinary journals. Substantial numbers of studies investigating “Unclassified Compounds” indicate both innovation in studying emerging contaminants and challenges in metadata standardization. We conclude that future advancements require leveraging multi-omics integration and sophisticated transgenic tools to transform the zebrafish from a screening model into a predictive platform for systems toxicology. By addressing current limitations in life-stage representation, chronic exposure paradigms, and translational validation, zebrafish research can fully realize its potential in shaping regulatory policies and advancing personalized toxicology.