The ubiquitous presence of pharmaceutical drugs and microbes in the water is leading to the development of drug resistant microbes. Therefore, efficient materials that can remove or inactivate the drug and microbe contaminants are required. In this work, nickel sulfide/calcium alginate (Ni3S4/CA), silver sulfide/calcium alginate (Ag2S/CA), modified titanium dioxide/calcium alginate (TiO2/CA), and Ni3S4/Ag2S/TiO2/calcium alginate (Ni3S4/Ag2S/TiO2/CA) aerogels have been synthesized for the removal of the oxytetracycline (OTC) drug and microbial contaminants from real beverage industry wastewater. The results revealed that Ni3S4/Ag2S/TiO2/CA aerogel is highly efficient for OTC adsorption and inactivation of microbes compared to Ni3S4/CA, Ag2S/CA and TiO2/CA aerogels. The OTC adsorption depends greatly on the solution pH, and optimum OTC removal was observed at pH 6 in its zwitterionic (OTC±) form. The formation of H-bonding and n-π electron donor-acceptors is possible to a considerable extent due to the presence of the double bond benzene ring, oxygen and nitrogen, sulfur-containing functional groups on the OTC molecules, and the Ni3S4/Ag2S/TiO2/CA aerogel. Based on the statistical analysis, root-mean-square deviation (RMSD), chi square (χ2) values, and higher correlation coefficient (R2) values, the Redlich–Peterson isotherm model and Elovich kinetic model are most suited to modelling the OTC adsorption onto Ni3S4/Ag2S/TiO2/CA. The prepared aerogels’ excellent antimicrobial activity is observed in the dark and with solar light irradiation. The zone of inhibition analysis revealed that the antimicrobial activity of the aerogels is in the following order: Ni3S4/Ag2S/TiO2/CA > TiO2/CA > Ag2S/CA > Ni3S4/CA, respectively. Moreover, the antimicrobial results demonstrated that reactive oxygen species, electrons, and active radical species are responsible for growth inhibition and killing of the microbes. These results indicated that Ni3S4/Ag2S/TiO2/CA aerogel is highly efficient in decontaminating pollutants from wastewater.