B IO-NANOTECHNOLOGY employing natural products is a promising approach for discovering and developing new drugs for treating various diseases. Chitosan (CH) is a natural product produced from crustacean shells. Recently, both CH and Chitosan nanoparticles (CH-NP) have been used in various pharmaceutical and biomedical applications owing to their unique properties. The main aim of this study was to determine the efficacy of CH and CH-NP in reducing the negative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in albino rats. Twenty adult male albino rats were divided into four groups of five rats each: the control (CTRL), TCDD, TCDD + CH, and TCDD + CH-NP groups. The activities of alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT), as well as total bilirubin, direct bilirubin, total protein, cholesterol, and triglycerides, all increased significantly in the TCDD-treated group. The serum albumin levels did not significantly change. Furthermore, histological, histochemical, and immunohistochemical analyses showed marked degeneration of liver tissue. Conclusion: Many prior dioxin-induced biochemical and histological changes improved when treated with CH or CH-NP, with no statistically significant differences between the CH and CH-NP groups.