Global healthcare systems face an enormous economic burden related to oxidative stress diseases and chronic wound treatments. Exploring therapies that regulate reactive oxygen species (ROS) within a non-toxic range could be promising in treating chronic wounds. Hence, this study synthesized the cerium oxide nanoparticles (CeO2 NPs) using endophytic Penicillium radiatolobatum. Further, the gum arabic-curcumin-CeO2 nanocomposites (GA-CU-CeO2 NCs) were prepared, characterized, and tested for enhanced antioxidant, anti-inflammatory, and wound healing effects. X-ray diffraction analysis revealed the cubic fluorite structure of GA-CU-CeO2 NCs. FT-IR analysis confirmed the presence of GA and CU in the GA-CU-CeO2 NCs. In TEM analysis, GA-CU-CeO2 NCs appeared in an average size of ∼25 nm with spherical and oval anisotropic structural distribution. DLS and ELS analysis indicated an average particle size and zeta charge of GA-CU-CeO2 NCs as 202 nm and −22.1 mV, respectively. The GA-CU-CeO2 NCs scavenged ABTS and DPPH radicals with an IC50 of 16.4 μg/mL and 56.0 μg/mL, respectively. Besides, GA-CU-CeO2 NCs did not induce apparent toxicity in NIH3T3 and RAW264.7 cells. GA-CU-CeO2 NCs attenuated the ROS-level and associated nucleus damage in H2O2-stressed RAW264.7 cells. GA-CU-CeO2 NCs indicated ∼90 % of wound gap closure of NIH3T3 cells within 36 h activity while being non-toxic to erythrocytes.