This study assesses groundwater quality in the western desert peripheries of El Minya Governorate, Egypt, through hydrochemical analysis, multivariate statistics, water quality indices (WQI), and health risk assessment. Twenty-four groundwater samples were collected and analyzed in July 2024. Results revealed high salinity (EC: 937–11,900 µS/cm), TDS (561–7140 ppm), and hardness (300–2000 ppm), exceeding WHO standards. Dominant hydrochemical facies include SO₄·Cl–Ca·Mg (56%), (SO₄·Cl–Na (33%), and 13% of sample located in the suture line, driven by evaporite dissolution and ion exchange. Principal Component Analysis (PCA) showed that salinity-related variables (Na⁺, Cl⁻, TDS) explained 50.8% of data variance. WQI results indicated that 25% of samples were "very poor" or "unfit for consumption," with the highest WQI value reaching 158. Agricultural evaluation found 7 samples unsuitable for irrigation, though most samples were suitable for cattle, but not always for poultry. Health risk assessment of Hofmeister ions showed that > 90% of samples exceeded safe intake limits for Ca, Na, Cl, and Mg. These levels pose risks for chronic kidney disease (CKD) and renal osteodystrophy (ROD). Overall, groundwater quality is significantly compromised by natural and anthropogenic influences, necessitating urgent treatment, monitoring, and sustainable management strategies.