Simultaneous degradation and detoxification during pharmaceutical and personal care product removal are important for water treatment. In this study, sodium niobate nanocubes decorated with graphitic carbon nitride (NbNC/g-C3N4) were fabricated to achieve the efficient photocatalytic degradation and detoxification of ciprofloxacin (CIP) under simulated solar light. NaNbO3 nanocubes were in-situ transformed from Na2Nb2O6•H2O via thermal dehydration at the interface of g-C3N4. The optimized NbNC/g-C3N4-1 was a type-I heterojunction, which showed a high conduction band (CB) level of −1.68 eV, leading to the efficient transfer of photogenerated electrons to O2 to produce primary reactive species, •O2−. Density functional theory (DFT) calculations of the density of states indicated that C 2p and Nb 3d contributed to the CB, and 0.37 e– transferred from NaNbO3 to g-C3N4 in NbNC/g-C3N4 based on the Mulliken population analysis of the built-in electric field intensity. NbNC/g-C3N4-1 had 3.3- and 2.3-fold of CIP degradation rate constants (k1 = 0.173 min−1) compared with those of pristine g-C3N4 and NaNbO3, respectively. In addition, N24, N19, and C5 in CIP with a high Fukui index were reactive sites for electrophilic attack by •O2−, resulting in the defluorination and ring-opening of the piperazine moiety of the dominant degradation pathways. Intermediate/product identification, integrated with computational toxicity evaluation, further indicated a substantial detoxification effect during CIP degradation in the photocatalysis system.