<p>Detergent contamination presents a growing concern in aquaculture due to its pronounced effects on bioaccumulation and the biochemical integrity of farmed fish. This review comprehensively synthesizes current evidence on detergent toxicity, emphasizing patterns of residue accumulation, oxidative stress mechanisms, and histopathological alterations observed in key aquaculture species. Detergent-derived surfactants compromise antioxidant defenses—particularly superoxide dismutase (SOD) and catalase (CAT)—leading to excessive reactive oxygen species (ROS) generation, lipid peroxidation, and pervasive cellular damage. These disruptions contribute to significant histopathological lesions that impair critical physiological functions such as respiration and metabolism. The complexities of detergent bioaccumulation, together with tissue-specific toxicity and oxidative pathways, highlight the vulnerability of cultured fish under continuous pollutant exposure. Despite mounting data on acute and subacute toxicity, major research gaps persist: the chronic, low-dose effects of long-term exposure are not fully addressed, and interactive impacts with other environmental contaminants remain poorly understood. Moreover, assessments of potential food safety risks for consumers are limited. Advancing this field requires more comprehensive, long-term studies that mimic realistic environmental scenarios, the adoption of robust oxidative stress and tissue biomarkers, and multi-faceted risk assessment frameworks. Integrating these approaches will enable more accurate ecological risk evaluations and guide the development of effective mitigation strategies supporting sustainable aquaculture. Ultimately, filling these knowledge gaps is essential not only to protect the health of farmed fish but also to ensure the safety of aquatic-derived food products for human consumption.</p>