Extensive research over the years has revealed the remarkable potential of gold nanoparticles (AuNPs) for detecting biomarkers in osteoarthritis (OA). AuNPs are a promising class of nanomaterials offering a wide range of diagnostic and clinical applications. It provides an effective and robust framework for qualitative and quantitative analysis of biomarkers present in the biological fluids of OA patients. AuNPs as theranostics have gained significant attention due to their discrete physical and optical characteristics, including localized surface plasmon resonance (LSPR), fluorescence, surface-enhanced Raman scattering, and quantized charging effect. These unique properties provide AuNPs as an excellent scaffold for ligand multiplexing, allowing accrued sensitivity for biomarker detection. Several reports have delved into the LSPR properties of the kinetics of biological interactions between the ligand and analyte. Tuneable radiative properties of AuNPs coupled with surface engineering allow facile detection of biomarkers in biological fluids. Herein, we have presented a comprehensive summary of distinct biomarkers generated from different molecular pathological processes in OA. An armamentarium of diagnostic methodologies such as aptamer conjugation, antibody coupling, ligand anchoring, and peptide decoration on the surface of AuNPs facilitates the identification and quantification of biomarkers. Additionally, a diverse range of sensing strategies for biomarker spotting, along with current challenges and future perspectives, have also been well delineated in the present manuscript.