Clinical treatment of endometriosis, a common gynaecological disorder, still remains a challenge. Hormonal suppression, pain relief medication and surgical intervention are the conventional treatment modalities; however, frequent recurrence of the disease renders the results unsatisfactory. Given the fact that oxidative stress, angiogenesis, excessive matrix degradation, and aromatase activity are associated with endometriosis, we were motivated to use the combinatorial effect of two drugs, Curcumin (Cur) and Letrozole (Let) encapsulated in PLGA and test their efficacy in mice induced with the disease. The nanoparticles (NPs) were synthesized using solvent evaporation method and characterization indicated the spherical particles to be monodispersed, polymorphic, small in size with high encapsulation efficiency, without having a tendency for significant aggregation or adhesion. Following standardization, 40mg/kg body weight of NPs was administered in endometriotic mice. Oxidative stress parameters, angiogenic markers, matrix degrading molecules, estrogen levels and endometriotic lesions, were assessed and compared before and after administration. Let-Cur NPs treatment in vivo, in addition to decreasing these parameters significantly, was also successful in reducing endometrial glands and micro-vessels density in the peritoneum to a considerable extent, thereby indicating significant regression of the disease. This is a proof of concept study. Pre-clinical non-human primate studies for testing the safety and efficacy of these NPs at larger doses in endometriosis is suggested. Citation: Jana SK, Chakravarty B, Chaudhury K (2014) Letrozole and Curcumin Loaded-PLGA Nanoparticles: A Therapeutic Strategy for Endometriosis.