Chronic kidney disease (CKD) is becoming a major public health problem worldwide, and excessive potassium intake is a health threat to patients with CKD. In this study, visible–shortwave near-infrared (Vis–SWNIR) spectroscopy and chemometric algorithms were investigated as nondestructive methods for assessing the potassium concentration in fresh lettuce to benefit the CKD patients' health. Interactance and transmittance measurements were performed and the competencies were compared based on the multivariate methods of partial least-square regression (PLS) and support vector machine regression (SVR). Meanwhile, several preprocessing methods [first- and second-order derivatives in combination with standard normal variate (SNV)] and wavelength selection method of competitive adaptive reweighted sampling (CARS) were applied to eliminate noise and highlight the spectral characteristics. The PLS models yielded better prediction than the SVR models with higher correlation coefficients (R²) and residual predictive deviation (RPD), and lower root-mean-square error of prediction (RMSEP). Excellent prediction of green leaves was obtained by the interactance measurement with R² = 0.93, RMSEP = 24.86 mg/100 g, and RPD = 3.69; while the transmittance spectra of petioles provided optimal prediction with R² = 0.92, RMSEP = 27.80 mg/100 g, and RPD=3.34, respectively. Therefore, the results indicated that Vis–SWNIR spectroscopy is capable of intelligently detecting potassium concentration in fresh lettuce to benefit CKD patients around the world in maintaining and enhancing their health.