Multi-drug resistance (MDR) infections are a significant global challenge, necessitating innovative and eco-friendly approaches for developing effective antimicrobial agents. This study focuses on the synthesis, characterization, and evaluation of cerium oxide nanoparticles (CeO2 NPs) for their antioxidant, anti-inflammatory, and antibacterial properties. The CeO2 NPs were synthesized using a Tribulus terrestris aqueous extract through an environmentally friendly process. Characterization techniques included UV-Visible spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray (EDX) analysis. The UV-Vis spectroscopy shows the presence of peak at 320 nm which confirms the formation of CeO2NP .The FT-IR analysis of the CeO2NP revealed several distinct functional groups, with peak values at 3287, 2920, 2340, 1640, 1538, 1066, 714, and 574 cm⁻¹. These peaks correspond to specific functional groups, including C-H stretching in alkynes and alkanes, C=C=O, C=C, alkanes, C-O-C, C-Cl, and C-Br, indicating the presence of diverse chemical bonds within the CeO2. XRD revealed that the nanoparticles were highly crystalline with a face-centered cubic structure, and SEM images showed irregularly shaped, agglomerated particles ranging from 100-150 nm. In terms of biological activity, the synthesized CeO2 NPs demonstrated significant antioxidant and anti-inflammatory properties. The nanoparticles exhibited 82.54% antioxidant activity at 100 μg/mL, closely matching the 83.1% activity of ascorbic acid. Additionally, the CeO2 NPs showed 65.2% anti-inflammatory activity at the same concentration, compared to 70.1% for a standard drug. Antibacterial testing revealed that the CeO2 NPs were particularly effective against multi-drug resistant strains, including Pseudomonas aeruginosa, Enterococcus faecalis, and MRSA, with moderate activity against Klebsiella pneumoniae. These findings suggest that CeO2 NPs synthesized via T. terrestris have strong potential as antimicrobial agents in addressing MDR infections.