The emergence of multidrug-resistant pathogens has intensified the search for eco-friendly and effective antimicrobial agents. The present study reports the green synthesis of zinc oxide nanoparticles (ZnONPs) using combined aqueous leaf extracts of Ziziphus oenoplia (L.) Mill. and Ziziphus mauritiana Lam. and evaluates their antioxidant, anti-inflammatory and antibacterial activities. Zinc oxide nanoparticles were synthesised by reacting the combined leaf extracts with 30 mM zinc sulfate under continuous stirring for 24–48 hr and were characterised using ultraviolet (UV)-visible spectroscopy. Antibacterial activity was assessed by agar well diffusion and time-kill curve assays against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas sp. The antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide, ferric reducing antioxidant power (FRAP), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and nitric oxide (NO) scavenging assays, while the anti-inflammatory potential was assessed using egg albumin denaturation and membrane stabilisation assays. The UV-visible spectra confirmed the formation of ZnONPs, with characteristic absorption peaks between 330 and 370 nm. The ZnONPs exhibited dose-dependent antibacterial activity, with maximum inhibition observed at 100 µg/mL. Time-kill assays demonstrated significant bactericidal effects over time. Antioxidant assays revealed strong free radical scavenging activity and reducing power, while anti-inflammatory assays showed effective inhibition of protein denaturation and membrane lysis. The results indicate that leaf-mediated ZnONPs possess multifunctional biological activities due to the synergistic effects of phytochemicals derived from both plants. These findings suggest that Ziziphus-derived ZnONPs hold promise as natural, biocompatible agents for wound healing and related biomedical applications.