The effect of hyper-mineral waters on human health has long been debated. This pilot study evaluated the influence of San Martino® water (Sardinia, Italy), on clinical and biological parameters, following the treatment of 10 hospitalized patients. Crenotherapy consisted of 1–2 L of the water daily for 10 days. A complete blood count, serum electrolytes, liver and kidney function tests, fasting lipid profile and plasma glucose, and abdominal ultrasound imaging were assessed before and at the end of treatment. In addition, body weight, dyspeptic symptoms, bowel movements, diuresis, uricuria and blood pressure were evaluated daily. According to its physico-chemical properties, the water is hyper-mineral (TDS 2808 mg/L) with a high content of bicarbonate and iron. At the end of the study, diuresis increased by 60% (850 vs 1295 ml/24 h, P = 0.009) and uricuria by 41% (362 vs 490 mg/24 h, P = 0.022) respectively, whereas plasma uric acid level decreased by 7% (4.7 vs 4.3 mg/dL, P = 0.043). Compared to the basal values, serum gamma-glutamyl transferase, alkaline phosphatase and total bilirubin levels, showed a reduction of 65% (31 vs 18 U/L, P = 0.022), 15% (96 vs 90 U/L, P = 0.041), and 11% (0.53 vs 0.45 g/dL, P = 0.041), respectively. Bowel movements improved in 62.5% of patients with constipation, and 80% of dyspeptic patients experienced symptoms relief. Compliance to the treatment reached 100%. Mild differences were observed in body weight and blood pressure, although not in ultrasound imaging during crenotherapy. These findings suggest that the San Martino® hyper-mineral water may have some benefits to human health. Additional studies with a larger-sized cohort and for a longer period are needed to confirm these preliminary results.