Background and objective Icodextrin is a novel, potentially advantageous peritoneal dialysis solution characterized by low glucose content and high molecular weight. This study aimed to compare the impact of icodextrin and glucose solutions on peritoneal dialysis patients. Methods This multicenter, prospective, randomized controlled trial included 40 peritoneal dialysis patients. Participants were randomized in a 1:1 ratio into an experimental group (icodextrin group) and a control group (glucose group). Both groups used 1.5% or 2.5% glucose dialysis solutions for three daytime exchanges. At night, the icodextrin group used 7.5% icodextrin, while the glucose group used 2.5% glucose solution. Patients were followed up bimonthly, assessing nighttime ultrafiltration, electrolytes, lipid and glucose profiles, albumin levels, and quality of life using the short form-36 health survey scale at 4 months. Results After 2 and 4 months, the icodextrin group demonstrated a considerably greater nighttime net ultrafiltration than the glucose group (P < 0.05). After 4 months, the icodextrin group exhibited lower serum sodium, chloride, and systolic blood pressure levels but higher calcium levels, albumin levels, and short form-36 health survey scores than the glucose group (P < 0.05). Conclusions Icodextrin enhances ultrafiltration, maintains electrolyte balance, and improves nutritional status in peritoneal dialysis patients. These effects contribute toward improvement in the patients’ quality of life. The protocol was registered at chictr.org.cn (Registration Number: ChiCTR2200062379).