Abstract: Pharmaceuticals and Personal Care Products (PPCPs) pollution has become a significant environmental concern due to their widespread presence in environmental media and potential ecological risks. Among these, Triclosan (TCS), a widely used antimicrobial in personal care products, is frequently detected in aquatic environments and poses growing ecological concerns; conventional risk assessment often assumes linearity, yet endocrine-active contaminants can elicit non-monotonic responses under environmentally relevant exposure. This study assessed acute (96 h, 200 and 400 µg/L) and chronic (30 d, 10, 100, and 500 ng/L) TCS toxicity in adult zebrafish (Danio rerio), targeting mortality, oxidative stress biomarkers (CAT and GSH-Px), lipid peroxidation (MDA), gill ultrastructure by scanning electron microscopy (SEM), and histopathology of liver and gonads, with one-way ANOVA/Tukey (P < 0.05). In acute exposure, TCS produced a dose- and time-dependent rise in mortality, reaching 50% at 400 µg/L after 96 h; CAT activity increased significantly, with a 41% elevation at 200 µg/L compared with the control, while 400 µg/L induced a weaker response, suggesting that moderate TCS levels more effectively activated the antioxidant defense system. Similarly, GSH-Px activity rose by 38% at 200 µg/L but declined at 400 µg/L, showing a consistent non-monotonic trend. MDA content increased by 29% at 200 µg/L but showed a smaller rise at 400 µg/L, indicating stronger lipid peroxidation under moderate exposure. In chronic exposure, CAT activity decreased by 43% and 45% at 10 and 500 ng/L, respectively, whereas the 100 ng/L group showed partial recovery, suggesting a non-monotonic “inverted U-shaped” response. In contrast, GSH-Px activity followed a “U-shaped” pattern, increasing by 32% at both 10 and 500 ng/L but remaining near control levels at 100 ng/L. Chronic exposure also altered lipid peroxidation, with MDA levels in the 500 ng/L group reduced by 42% compared with the control, differing from the acute pattern and implying altered metabolic regulation under long-term exposure. Scanning electron microscopy of gills revealed epithelial lifting, lamellar fusion, and surface roughness under both acute and chronic treatments, while histopathology showed hepatic vacuolization, nuclear pyknosis, and gonadal lesions, including reduced oocyte maturation and abnormal spermatogenesis. These findings demonstrate that TCS induces oxidative stress, disrupts tissue integrity, and impairs reproductive function through non-monotonic dose–response relationships, with moderate concentrations often exerting stronger effects than higher levels. Collectively, the results provide mechanistic evidence of TCS toxicity in aquatic organisms and emphasize the ecological risks associated with environmentally relevant exposures, underscoring the need for stricter regulation and monitoring of this contaminant.