Peritoneal dialysis (PD) represents an essential renal replacement therapy for end-stage renal disease patients. However, conventional glucose-based dialysis solutions limit the clinical adoption of PD due to complications including peritoneal fibrosis and metabolic disturbances. This review systematically elaborates on advances in novel biocompatible osmotic agents: L-carnitine improves peritoneal metabolic homeostasis, while hyperbranched polyglycerol enables sustained ultrafiltration with dual peritoneal/renal protection. These innovations delineate the future direction for osmotic agent development: integrating multifunctional properties (anti-fibrotic, pro-repair, and metabolic regulation) beyond foundational osmotic efficacy.