Background: Gut microbiota (GM) plays a crucial role in obesity pathophysiology and is heavily influenced by dietary factors. Polyphenols have shown a positive effect in preventing and treating obesity, which is blunted in the absence of GM. Pomegranate peel, known for its high content of polyphenols (ellagitannins), has been found to exhibit favorable metabolic effects in obesity. Interestingly, ellagitannins are metabolized by the action of GM. However, the specific impact of pomegranate peel extract (PPE) on GM and metabolism remains unclear. Objective: to evaluate the effect of a PPE (microencapsulated or not) on the composition of GM in high-fat diet (HFD)-fed mice and analyze its association with metabolic parameters. Methods: Male C57BL/6J mice (n = 40) were randomly distributed into five groups: control diet (CD), HFD, HFD + inulin (IN), HFD + PPE (50 mg/kg/d of total polyphenols; TP), and HFD + MPPE (50 mg/kg/d TP), for 14 weeks. Liver and serum antioxidant status were assessed. GM composition, further relative abundances, and biodiversity were calculated from cecal content samples. The bacterial community clustering was analyzed using a canonical-correlation analysis (CCA). GM parameters and metabolic outcomes were evaluated for correlation (Spearman ' s correlation), p < 0.05. Results: PPE and MPPE showed increased energy expenditure, reduced liver arachidonic acid content, elevated antioxidant capacity, and higher GM alpha diversity compared to HFD alone. Conclusion: PPE, regardless of encapsulation, ameliorated metabolic alterations induced by HFD, potentially through modulation of GM. These findings provide data on the therapeutic potential of PPE in managing obesityrelated metabolic dysfunction.