Antimicrobial photodynamic therapy (aPDT) is a high potential strategy for the treatment of microbial infections in endodontics. In this study, a novel antibacterial agent was designed and prepared based on the two morphologies of zinc oxide nanomaterials (NMs) as ZnO nanosphere (ZnOS) and ZnO nanorod (ZnOR). Their surfaces were coated with carnosine (CAR)-functionalized polycyclodextrin (ZnO@PCD-CAR) for higher payload of curcumin (CUR) as a photosensitizer (PS). This system was characterized using FT-IR, XRD, TGA, FE-SEM, zeta potential analysis and UV-visible spectroscopy. The colony forming unit (CFU) assay was carried out to evaluate the antimicrobial properties of the nanoformulations againts Enterococcus faecalis (E. Faecalis). The target products (ZnOS@PCD-CAR/CUR and ZnOR@PCD-CAR/CUR) exhibited a light stability approximately by 2.9 and 2.8 fold, respectively, higher than the free CUR. Compared to the bare CUR, these materials indicated more stability againts pH variations. ZnOS@PCD-CAR/CUR and ZnOR@PCD-CAR/CUR NMs-mediated aPDT, significantly declined the count of E. Faecalis strains about 1.5 and 2 log (P < 0.05). Due to the high CUR loading, proper stability and significant inhibitory effects against E. Faecalis, ZnO@PCD-CAR/CUR could be considered as a promising antimicrobial agent in aPDT for efficient treatment of root canal infections.