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Endometriosis is a common, chronic gynecological disorder associated with ongoing pelvic pain, infertility, and adhesions in reproductive age women. Current therapeutic strategies are not effective and the recurrent nature of endometriosis makes it difficult to treat. In this study, we have designed a drug delivery system to control sustained and prolonged release of curcumin in the peritoneum and pelvic cavity of a mouse model of endometriosis. Poly ε-Caprolactone (PCL) and poly ethylene glycol (PEG) polymers were used to synthesize curcumin loaded nanofibers. After scanning electron microscopy (SEM) observation of the nanofiber's morphology, we evaluated the drug release profile and in vitro degradation rate of the curcumin-loaded nanofibers. Next, we tested these nanofibers in vivo in the peritoneum of an endometriosis mouse model to determine their anti-endometriosis effects. Histological evaluations were also performed. Curcumin loaded nanofibers were successfully synthesized in the 8 and 10 wt% polymers. The release test of the curcumin-loaded nanofibers showed that approximately 23% of the loaded curcumin was released during 30 min, 35% at 24 h, and 50% at 30 days. Endometriosis was successfully induced in Balb/c mice, as noted by the observed characteristics of endometriosis in all of the mice and confirmation of endometriosis by hematoxylin and eosin (H&E) staining. In vivo experiments showed the ability of these implanted curcumin loaded nanofibers to mitigate endometriosis. We observed a considerable reduction in the endometrial glands and stroma, along with significant reduction in infiltration of inflammatory cells. Implantable curcumin loaded nanofibers successfully mitigated intraperitoneal endometriosis. [ABSTRACT FROM AUTHOR]