Hypertension is a major public health issue contributing to the global burden of disease and often leading to renal complications. Plectranthus ornatus is traditionally used to treat hypertension, despite limited scientific evidence supporting its efficacy. This study investigated the histological and biochemical effects of Plectranthus ornatus extract on the renal system of dexamethasone-induced hypertensive rabbits. A total of 20 rabbits were divided into four groups. The negative control group (n = 6) received a saline injection; the positive control group (n = 6) received a dexamethasone injection; and two dexamethasone-injected groups (n = 4 each) were treated with 200 and 1,000 mg/kg of the extract for a period of 14 days. Histological and biochemical investigations were carried out using standard techniques. Increased systolic and diastolic blood pressure was observed in hypertensive animals induced with dexamethasone (2 mg/kg) in 5% sodium chloride solution. Histological examination showed mild renal inflammation attributable to the high blood pressure. Following extract administration, there was a dose-dependent decrease in blood pressure at both 200 mg/kg and 1,000 mg/kg doses administered by oral gavage. Electrolytes (Na⁺, K⁺, Cl⁻, HCO_₃⁻), as well as urea and creatinine levels, remained within acceptable ranges, including in animals administered with the low-dose extract. In addition, the extract produced observable histological changes, particularly at higher doses, without significant impairment of kidney and bladder structure, although these positive changes require further investigation to better understand their implications. These findings suggest that the Plectranthus ornatus extract has potential antihypertensive and nephroprotective effects; however, careful optimization of dosage and treatment duration is necessary to minimize adverse effects. Further research is recommended to confirm its long-term safety and efficacy.