Abstract Objectives High sodium intake is a major risk factor for hypertension and renal diseases. Previous studies have shown that a suspension of ethanolic extract of Psidium guajava (guava) leaves (PsE) has antihypertensive effects in rats on a high-sodium diet (HSD), but some mechanisms to that remain unexplored. This study explored whether oral PsE treatment affects sodium handling by the intestine and alters the gut microbiome in HSD-fed rats. Methods Male Wistar rats were divided into two groups: standard salt diet (SSD) and HSD (0.9% Na+), from weaning. After 12 weeks, both groups received PsE (200 mg/kg) or a vehicle for an additional 4 weeks. Key findings Sodium excretion was measured using flame photometry, and sodium absorption was assessed by intestinal perfusion technique. The gut microbiome was analysed through 16S ribosomal gene sequencing. HSD increased faecal sodium, further elevated by PsE, which inhibited intestinal sodium absorption in HSD rats. HSD altered the abundance of specific bacterial families, which PsE partially reversed. No changes in alpha diversity were noted among groups. Conclusions These findings suggest that PsE inhibited intestinal sodium handling and that PsE, combined with increased faecal sodium, may reshape the gut microbiome of HSD rats to resemble that of SSD rats.