The widespread use of antimicrobial agent triclosan (TCS) poses significant health risks to both aquatic organisms and humans. The research on its neurotoxicity and underlying mechanisms is, however, limited. Here we first conducted a 32-day exposure experiment with five TCS concentrations (10, 30, 60, 90 and 120 µg/L) to investigate its impact on overall gene expression in Rana omeimontis larvae. Transcriptomics analysis unveiled a strong dose-dependent pattern of gene expression alterations, with a distinct transcriptomic shift observed in the T030 (30 µg/L) group. In addition, neurodegenerative disease pathway and oxidative stress response GO (gene ontology) terms were found to be highly enriched across the regulated genes in all TCS-exposed groups, suggesting potential TCS-induced neurotoxicity. To further explore this, we performed a 40-day experiment with a low (30 µg/L) or high (90 µg/L) TCS concentration. Morphological assessments revealed that TCS-exposed larvae exhibited developmental and growth inhibition. Using RT-qPCR and immunohistochemical analysis, we confirmed that TCS exposure induced neurotoxicity and triggered neurodegenerative diseases as suggested by Tau protein aggregation in the midbrain. Consistent with these findings, TCS-exposed larvae displayed abnormal behaviors. Our study thus for the first time presents a comprehensive assessment of the adverse effects of TCS exposure on amphibian larvae, encompassing morphological, biochemical, and physiological aspects. Notably, we identified RNF112 and Tau as potential molecular targets that may mediate TCS-induced neurotoxicity. These findings advance the knowledge on how organisms respond to environmental changes and highlight the importance of further investigation into the potential neurotoxicity of TCS within aquatic ecosystems and its implications for human health.