A near-infrared (NIR) light-driven NaYF:Yb/Er-TiO-TiC (NYF-TiO-TiC) heterostructure-based photoelectrochemical (PEC) biosensing platform was constructed for highly sensitive d-serine (d-ser) detection. Accurate d-ser detection depends on the model biocatalyst, d-amino acid oxidase (DAAO), which converts d-ser into hydroxypyruvate and an equimolar concentration of hydrogen peroxide (HO) via an enzymatic reaction. The TiO-TiC semiconductor and NaYF:Yb/Er optical transducer formed a Schottky junction that provided an irreversible channel for electron transfer. Infrared light was converted into absorbable multiemission light, thereby effectively increasing light absorption. Simultaneously, the generated HO rapidly scavenged photogenerated holes to separate electron-hole pairs, which amplified the photocurrent signal. Under optimal conditions, the NIR light-driven PEC biosensor exhibited an excellent PEC performance for d-ser detection, with a wide linear range of 2-1650 μmol L and detection limit as low as 0.286 μmol L. Importantly, high detection reproducibility and accuracy were achieved using this strategy for analyzing human serum and rat cerebrospinal fluid (CSF) specimens. The admirable applicability of the NYF-TiO-TiC-based PEC biosensor for detecting d-ser may lead to further opportunities for detecting other disease-related biomarkers.