Background: Hemodialysis patients often develop constipation due to dietary restriction and the use of phosphate and/or potassium binders. Lubiprostone is a novel laxative that promotes defecation by activating the chloride ion channel 2 (ClC-2) in the gastrointestinal tract. While lubiprostone has been reported to be useful in bowel control of dialysis patients, no studies have examined changes in electrolyte levels following administration of lubiprostone. Methods: We prospectively compared stool frequency and electrolyte levels before and after treatment with lubiprostone in 28 hemodialysis patients treated with the drug for at least 3 months in our hospital. Results: Mean ± standard deviation of stool frequency was significantly increased from 1.8 ± 1.3 times/week before treatment to 4.3 ± 1.8 times/week at Month 1, 4.9 ± 1.9 times/week at Month 2, and 4.5±1.5 times/week at Month 3 (p < 0.001, p < 0.001, and p < 0.001, respectively). With regard to electrolyte levels, only serum inorganic phosphorus (IP) level was significantly decreased, from 4.7 ± 1.5 mg/dL at baseline to 4.5 ± 1.6 mg/dL at Month 1, 4.0 ± 1.3 mg/dL at Month 2, and 3.8 ± 1.1 mg/dL at Month 3 (p = 0.123, p < 0.001, and p < 0.001, respectively). Lubiprostone not only improved bowel control, but also decreased serum IP levels in hemodialysis patients. Conclusions: Lubiprostone may improve prognosis of hemodialysis patients through bowel control and a decrease in serum IP.