Background: Peritoneal dialysis (PD) is an established kidney replacement therapy, but long-term exposure to bioincompatible dialysate, uremic toxins, recurrent peritonitis, glucose degradation products, oxidative stress, and sterile inflammation progressively remodels the peritoneal membrane and contributes to peritoneal fibrosis (PF). This review summarizes the molecular basis of PF in PD and evaluates the therapeutic rationale for incretin-based interventions beyond weight loss and glycemic control. Methods: This narrative review synthesizes mechanistic, translational, and clinically relevant literature on PD-associated PF, with emphasis on DPP-4 biology, GLP-1 receptor agonism, inflammatory and oxidative signaling, angiogenesis, mesothelial-to-mesenchymal transition, glycemic management in PD, and selected author-conducted translational studies interpreted alongside independent evidence. Results: Available evidence supports a model in which DPP-4 activation, altered GLP-1/GLP-1R signaling, TGF-β/Smad3-driven mesothelial transition, NF-κB/MyD88 inflammation, ROS-mediated oxidative stress, angiogenesis, apoptosis, and cytoskeletal remodeling converge to impair peritoneal membrane integrity. DPP-4 inhibition, exendin-4, and dulaglutide attenuated these pathways in experimental models, while GLP-1 receptor agonists have established metabolic benefits in appropriate diabetic and obese populations. Conclusions: Direct clinical evidence that incretin-based therapies prevent or treat peritoneal fibrosis in humans undergoing PD is currently lacking. Therefore, peritoneal membrane protection, reduced ultrafiltration failure, and improved technique survival should be regarded as investigational, hypothesis-generating possibilities that require prospective clinical validation.