The increasing prevalence of chronic metabolic disorders, environmental toxicant exposure, and oxidative stress-related diseases necessitates the exploration of natural bioactive compounds with therapeutic potential. Pomegranate (Punica granatum), rich in polyphenols such as ellagitannins and punicalagin, has emerged as a promising candidate due to its multifaceted pharmacological properties. This research synthesizes evidence from cellular, clinical, and in vivo experimental models, particularly zebrafish (Danio rerio), to evaluate the antioxidant, anti-inflammatory, and protective effects of pomegranate-derived compounds. Studies indicate that pomegranate juice and extracts significantly modulate inflammatory signaling pathways in colon cancer cells and exhibit anti-proliferative activity. Clinical trials demonstrate improvements in glycemic control, cardiovascular health, and inflammatory biomarkers following dietary supplementation. Concurrently, zebrafish models provide valuable insights into toxicological responses, revealing the impact of environmental pollutants such as microplastics, endocrine disruptors, and xenobiotics on physiological systems. The integration of pomegranate interventions within these models suggests potential mitigation of oxidative stress, hepatic steatosis, and neurotoxicity. This paper critically evaluates the mechanistic pathways underlying these effects, including modulation of reactive oxygen species, cytokine expression, and metabolic regulation. Furthermore, it addresses methodological challenges, translational limitations, and future research directions. The findings support the hypothesis that pomegranate-derived compounds may serve as effective nutraceuticals in combating toxicity-induced pathologies and chronic diseases.