This work presents a green synthesis route, which utilises extracts from an indigenous plant in South Africa, eastern and southern Africa that is understudied and underutilised, for preparing zinc oxide nanoparticles (ZnO NPs). This study involved optimisation of the green synthesis method using Leonotis ocymifolia (L.O.) extracts and performing comparative studies on the effects of using different zinc (Zn) salt precursors; zinc sulphate heptahydrate (Z001) and zinc acetate dihydrate (Z002) to synthesise the ZnO NPs. The comparative studies also compared the L.O-mediated ZnO NPs and chemical-mediated ZnO NPs (Z003). The as-prepared ZnO NPs were tested for their effectiveness in the photodegradation of methylene blue (MB) dye. Furthermore, antibacterial studies were conducted using the agar well diffusion method on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. The structural, morphological, and optical characteristics of the synthesised ZnO NPs were analysed using XRD, FTIR, SEM, EDS, DRS, and BET techniques. The XRD results indicated that the L.O-mediated ZnO NPs had smaller crystallite sizes (18.24–19.32 nm) than their chemically synthesised counterparts (21.50 nm). FTIR confirmed the presence of biomolecules on the surface of the L.O-mediated NPs, and DRS analysis revealed bandgap energies between 3.07 and 3.18 eV. The EDS results confirmed the chemical composition of the synthesised ZnO NPs, which were made up of Zn and O atoms. Photocatalytic studies demonstrated that the L.O-mediated ZnO NPs (Z001) exhibited a superior degradation efficiency of the MB dye (89.81%) compared to chemically synthesised ZnO NPs (56.13%) under ultraviolet (UV) light for 240 min. Antibacterial tests showed that L.O-mediated ZnO NPs were more effective against S. aureus than E. coli. The enhanced photocatalytic and antibacterial properties of L.O-mediated ZnO NPs highlight their potential for environmental remediation and antimicrobial applications, thus supporting sustainable development goals.