Background and Objectives: Endothelial dysfunction represents an early indicator of cardiovascular disease in individuals with hypertension. Leptin, an adipokine that regulates vascular homeostasis and metabolism, has been linked to vascular impairment; however, its relationship with vascular reactivity in hypertensive patients remains unclear. Materials and Methods: A cross-sectional study was conducted involving 100 hypertensive patients recruited from the cardiovascular outpatient clinic of Hualien Tzu Chi Hospital between January and July 2021. Clinical profiles, anthropometric data, and laboratory results were collected. Endothelial function was evaluated through digital thermal monitoring, with vascular reactivity index (VRI) classified as poor (<1.0), intermediate (1.0–1.9), or good (≥2.0). The association between serum leptin levels and VRI was examined using correlation analysis, multivariable logistic regression, linear regression, and receiver operating characteristic (ROC) analysis. Results: Of the 100 participants, 10 (10%) exhibited poor VRI, 46 (46%) had intermediate VRI, and 44 (44%) had good VRI. Patients with impaired VRI were significantly older (p = 0.015), had higher waist circumference (p < 0.001), and showed higher serum leptin concentrations (p < 0.001). Multivariable logistic regression identified leptin as an independent factor associated with vascular reactivity dysfunction (OR = 1.096, 95% CI: 1.025–1.171, p = 0.007) and poor vascular reactivity (OR = 1.197, 95% CI: 1.034–1.387, p = 0.016). Serum leptin levels were negatively correlated with VRI (r = −0.408, p < 0.001), and stepwise linear regression confirmed leptin as an independent determinant of VRI (β = −0.296, p = 0.001). ROC analysis further demonstrated that leptin could predict vascular reactivity dysfunction (AUC = 0.724, 95% CI: 0.625–0.824, p < 0.001) and poor vascular reactivity (AUC = 0.770, 95% CI: 0.606–0.932, p = 0.0012). Conclusions: Higher serum leptin levels are independently associated with impaired vascular reactivity in hypertensive patients. Leptin may therefore serve as a potential biomarker for early impairment of vascular reactivity in this population.