Antibiotic residues in wastewater cause a serious threat to aquatic environment and human safety. Therefore, the development of robust strategies for detecting antibiotic residues becomes critical. In this work, a surface-enhanced Raman scattering (SERS) substrate, consisting of gold nanoparticles/nano diamond/carbon nitride (Au/ND/C3N4) hybrid, which features enhanced light utilization and self-cleaning properties, is developed for sensitive sensing of tetracycline. The fabricated Au/ND/C3N4 substrate effectively captures target molecules and enhances Raman activity, owing to abundant functional groups and light scattering effect of ND. Moreover, the heterostructure formed by Au NPs, ND and C3N4 endows this SERS substrate with superior self-cleaning capability, enabling its reusability. The Au/ND/C3N4 substrate exhibits high sensitivity (10-14 M), desirable reproducibility (RSD = 13.29 %, n = 238) and favourable stability (84.8 % of initial intensity after 30 days) for crystal violet probe. Also, no significant loss of SERS or catalytic activity is observed during cyclic SERS detection. Likewise, the detection of tetracycline at nanomolar level is achieved with good recyclability. This work proposes a distinctive strategy for enhancing SERS activity, and the developed self-cleaning Au/ND/C3N4 substrate represents a potential candidate for highly sensitive detection of antibiotic residues in wastewater.