In the recent decade, zinc oxide nanoparticles (ZnO NPs) have been widely explored owing to their versatile properties and prodigious demands in the drug delivery, medical, energy storage, cosmetics, and the healthcare sectors. Therefore, the current work opts for an environmentally benign method to prepare ZnO NPs. The leaf extract of Calendula officinalis L. acts as a reducing agent for the metal ions; therefore, in the current research, ZnO NPs were prepared via green route by using Calendula officinalis leaf extract. Furthermore, the ZnO NPs were analysed with different spectroscopic techniques to confirm the structure and stability of nanomaterials. The prepared ZnO NPs were characterized by XRD, FE-SEM, FT-IR and UV–Vis studies. Also, the antioxidant and antimicrobial properties of the synthesized ZnO NPs were investigated. The XRD result of synthesized ZnO NPs showed the crystalline size 28.23 nm with wurtzite hexagonal structure along with the most intense peak (101). Following preliminary confirmations of the intended ZnO NPs, both big and small agglomerated forms were observed in the FE-SEM, which is often used to determine their exterior assembly. Further, the results of Fourier transform infrared spectroscopy (FT-IR) indicated the formation of pure ZnO NPs with an absorption peak of the Zn–O bond between 4000 cm−1 and 500 cm−1 and no discernible peak in the monitoring range. The UV–Vis spectrum of the green synthesized ZnO NPs were revealed two prominent absorption peaks at 355 nm and 370 nm with energy band gap of 2.986 eV. Using the 1, 1-di phenyl-2-picrylhydrazyl (DPPH) test, the antioxidant activity of the described ZnO NPs was assessed. It demonstrated how, ZnO NPs significantly increased their antioxidant activity by scavenging 1, 1-di phenyl-2-picrylhydrazyl (DPPH) free radicals. It could be seen that synthesis of the naturally occurring plant product ZnO NPs have been acting as an alternate of chemical antioxidant. The antimicrobial analysis was also performed with the help of disk diffusion method where three multi-drug resistant human pathogens namely Staphylococcus aureus, Klebsiella pneumoniae and E.coli were used. The Zone of Inhibition diameter values are 35.2 mm ± 0.9, 23.6 mm ± 0.1 and 13.5 mm ± 0.1, respectively, which showed that the ZnO NPs was highly effective against S. aureus. Thus, the green synthesis method of ZnO NPs using leaf extract of Calendula officinalis is evidence that it is superior and environmentally friendly method for the preparation of ZnO NPs and hence it can be utilized in various nano-medicine approaches.