Phytofabricated green synthesis of zinc oxide (ZnO) nanoparticles using different plant extracts of Azadirachta indica, Hibiscus rosa-sinensis, Murraya koenigii, Moringa oleifera, and Tamarindus indica for biological applications has been reported. ZnO nanoparticles were also synthesized by chemical method to compare the efficiency of the green synthesized nanoparticles. FT-IR spectra confirmed the functional groups involved in the green synthesis of ZnO nanoparticles and the powder XRD patterns of the ZnO nanoparticles revealed pure wurtzite structure with preferred orientation at (100) reflection plane. SEM and TEM analysis revealed the spherical shape of the synthesized ZnO nanoparticles with the particle size between 54 and 27 nm. The antioxidant activity was evaluated by five different free radical scavenging assays. The present study also intends to screen α-amylase and α-glucosidase activity of ZnO nanoparticles synthesized using natural sources, which may minimize the toxicity and side effects of the inhibitors used to control diabetes. The ZnO nanoparticles synthesized using T. indica extract displayed remarkable antioxidant and antidiabetic activities.