Nanoparticles of zinc oxide (ZnO NPs) were synthesized through a sustainable chemistry approach using aqueous extracts from Colocasia esculenta leaves. Characterization was conducted using UV-Visible spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR). Statistical analysis of antimicrobial activity data was carried out using Social Package for Social Sciences (SPSSS) version 20, with results reported as mean ± standard deviation (Mean ± SD). One-way Analysis of Variance (ANOVA) with Least Significance Difference (LSD) post hoc tests were performed at significance level (p < 0.05). Optimal nanoparticle formation occurred at 0.50 mol/dm³ ZnO solution at 80 °C over a 4-hour reaction period. The synthesized ZnO NPs exhibited a hexagonal wurtzite crystal lattice structure with an mean particle size of approximately 12 nm. FTIR analysis showed phenolic compounds, amines, peptides, and amides, which facilitated reduction of zinc ions, capping, and stabilization of the ZnO NPs. The ZnO NPs demonstrated concentration-dependent antimicrobial effects against five fungal pathogens (Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Fusarium oxysporum, and Botryodiplodia theobromae,) and three bacterial strains (Klebsiella oxytoca, Serratia marcescens, and Pseudomonas aeruginosa). Their inhibitory efficiency ranged from 32.22% to 89.95%, showing comparable performance to standard antimicrobial agents such as clotrimazole and ciprofloxacin. These findings suggest that ZnO NPs synthesized from Colocasia esculenta have promising applications in postharvest disease management and pharmaceutical development.