Luteolin is a natural flavone with various beneficial properties. We hypothesise that luteolin could alleviate haemodynamic, vascular, and renal changes caused by renal artery stenosis in rats. Male Sprague-Dawley rats were randomly divided into five groups (n = 8/group): Sham, two-kidney, one-clip (2K1C), 2K1C + luteolin (25 or 50 mg/kg/day), 2K1C + lisinopril (5 mg/kg/day). Hemodynamic parameters, vascular-kidney function and morphology were evaluated. Luteolin treatment for four weeks markedly alleviated hemodynamic changes, mitigated sympathetic nerve overactivity and ameliorated endothelial dysfunction in 2K1C rats. Aortic hypertrophy and remodelling, evident by increases in cross-sectional areas, aortic wall-to-lumen ratio, and fibrotic areas in 2K1C rats, were relieved by luteolin treatment (p < 0.05). Luteolin alleviated renal injuries, restored glomerular filtration rate, decreased urinary α-1-microglobulin levels, and attenuated renal fibrosis in 2K1C rats (p < 0.05). It reduced superoxide production, protein carbonyl, malondialdehyde, tumour necrosis factor-α, and interleukin-6 concentrations, but raised superoxide dismutase and catalase activities in 2K1C rats (p < 0.05). Luteolin mitigated the overexpression of α-smooth muscle actin, vascular cell adhesion molecule-1, transforming growth factor-β1/Smad2/3, and nuclear factor-κB proteins in aortic tissue. In addition, the overexpression of the JAK2/STAT3 pathway in a non-clipped kidney was suppressed by luteolin treatment (p < 0.05). Lisinopril has shown advantageous effects on vascular and renal abnormalities, akin to those of luteolin. In summary, luteolin improved haemodynamic alterations and vascular and renal impairment in 2K1C rats by attenuating oxidative stress, inflammation, and fibrotic signalling pathways, suggesting its potential as a promising therapeutic candidate for renal artery stenosis-induced vascular and renal injury.