This study describes the use of banana peel (BPEs) and date seed extracts (DSEs) as waste products in the sustainable and eco-friendly biological synthesis of zinc oxide nanoparticles (ZnONPs). ZnONPs_BPE and ZnONPs_DSE were characterized using an ultraviolet-visible spectrophotometer (UV-VIS), Scanning (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential analysis, and Fourier transform infrared (FTIR) spectroscopy. Moreover, the biocompatibility of ZnONPs was analyzed against the normal human skin fibroblast (HSF) cell line. Peaks of UV spectra were 300 nm and 400 nm for ZnONPs-BPE and for ZnONP _DSE, respectively, confirming the ZnONPs’ formation. XRD revealed their hexagonal structure. SEM showed the nanocrystals of ZnONPs_BPE, which are interlinked to one another in a uniform shape, while ZnONPs_DSE appear as large and small chunky crystals. The mean size of ZnONPs_BPE and ZnONPs_DSE was 50 nm and 62 nm using TEM, respectively. On the contrary, their mean size was bigger using DLS with the zeta potential of ZnONPs_BPE = −12.7 mV and ZnONPs_DSE = −5.69 mV. The FTIR analysis demonstrated the presence of carboxyl, hydroxyl, and C–H of cellulose, hemicelluloses, and lignin polymers on ZnONPs surfaces that act as reducing, capping, and stabilizing agents. ZnONPs_BPE (IC50 > 100) have lower cytotoxic effects on HSF cells than ZnONPs_DSE (IC50 = 29.34 μg/mL). The present study indicates the successful synthesis of ZnONPs using agro-wastes that could help in waste management and recycling. Furthermore, ZnONPs_BPE is safe to use for further applications.