Photocatalysts with high efficiency in water and wastewater treatment have gained increasing attention in recent years. This study synthesized an In2O3/NiO/MoS2 composite using the hydrothermal method and characterized its crystal structure, particle size, morphology, elemental purity, and optical properties. This nanocomposite exhibits high photocatalytic activity under visible light radiation. It achieved efficiencies of 91.57% and 88.23% in decomposing Imatinib and 5-fluorouracil, respectively. The formation of heterogeneity between MoS2 and NiO enhances the photocatalytic activity, which facilitates the separation and transfer efficiency of photo-generated electron-hole pairs, increases the catalytic active sites, and inhibits the rate of electron-hole recombination. The photocatalytic mechanism shows that both O2− and H+ are reactive species for the degradation of the studied pollutant. The stability and reusability tests deposited that the In2O3/NiO/MoS2 composite photocatalyst has superior stability during four reuse cycles. The results of the study show that a unique photocatalyst system can provide a new perspective and create new opportunities for the design of efficient composite photocatalysts.