The presence of pharmaceutical residues notably antibiotics in the environment is an increasing concern due to their persistence and toxicity. Developing efficient and eco-friendly methods to eliminate antibiotic residues from water bodies has become a major environmental challenge. CeO2 doped with a heteroatom forms a hybrid structure with g-C3N4 and could serve as an efficient photocatalytic agent. In this study, CeO2/g-C3N4 and Ag2O/CeO2/g-C3N4 hybrid catalysts were prepared for UV light degradation of ciprofloxacin (CIP) antibiotic. The various factors that influence the degradation were experimentally optimized. The kinetics of the degradation was investigated using the Langmuir–Hinshelwood kinetic model. The effect of three operational parameters influencing the photocatalytic degradation has been evaluated using Box–Behnken design of response surface methodology. The highest degradation of CIP was observed at CIP concentration of 10 μg/L with a catalyst amount of 30 mg after 2.5 h. Efficient charge separation was achieved from the dopant and the existing integrated electric field of the heterojunction showed impressive higher activity.