Water pollution poses an increasingly dire threat to both public health and the environment, with antibiotics emerging as significant chemical contaminants. Their pervasive presence in the environment exposes microorganisms, particularly bacteria, to the risk of evolving resistance. Antibiotic pollution disrupts natural food chains and exacerbates other environmental challenges. This study focuses on the utilization of TiO2-based photocatalysts to break down amoxicillin, azithromycin, and penicillin under various conditions. The TiO2 nanoparticles (NPs) underwent comprehensive characterization using various techniques. X-ray diffraction (XRD) revealed a tetragonal structure, while Ultraviolet-Visible Diffuse Reflectance Spectroscopy (UV-DRS) unveiled the energy bandgap in the UV region. Field Emission Scanning Electron Microscope (FE-SEM) and Transmission Electron Microscope (TEM) images depicted a spherical morphology. X-ray photoelectron spectroscopy (XPS) analysis delved into the spin-orbit components. The study investigated the impact of physical parameters like pH, temperature, time, and agitation rate on the photocatalytic degradation of these antibiotics by TiO2NPs. pH exerted a significant influence on degradation, with rates reaching 84.12%, 73.96%, and 78.35% at pH 9 after 60 minutes for amoxicillin, azithromycin, and penicillin respectively. Temperature demonstrated dependency, with degradation rates of 62.34%, 77.92%, and 78.32% observed at 40°C after 60 minutes. Agitation at 160 rpm enhanced degradation, achieving rates of 84.12%, 78.54%, and 79.12% for the same duration. This highly efficient process shows great promise for effectively removing antibiotic pollutants from wastewater.