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Multi-doped photocatalysts are among the new class of materials employed for photocatalysis and as an antimicrobial agent. Lower band gap energy due to the metal dopant and lower electron–hole recombination because of non-metal dopant increase the overall efficiency of photocatalyst. Furthermore, these dopants directly influence optical shift, crystallinity and surface area. A Ni, C, N, S multi-doped ZnO photocatalyst was synthesized by simple hydrothermal co-precipitation method by using thiourea as a non-metal precursor and was characterized by XRD, SEM, TEM, EDAX, FTIR techniques. Ni, C, N, S dopants were detected in EDAX, FTIR and XRD. The average particle size was found 12.82 nm from particle size distribution studies, TEM and XRD analysis. The synthesized catalyst showed highest photocatalytic efficiency of Indigo Carmine dye at higher pH and minimum catalyst dose in 120 min of solar light exposure by obeying pseudo first order kinetics. Furthermore, the catalyst was reused for multiple degradation cycles and reusable up to four cycles. Ni, C, N, S multi-doped ZnO photocatalyst was also employed as an antimicrobial agent and showed higher antimicrobial activity against Escherichia coli and Staphylococcus saprophyticus pathogenic bacteria at different concentrations. [ABSTRACT FROM AUTHOR]