Background <p>Auditory brainstem response (ABR) tests have demonstrated that the peripheral auditory sensitivity of the red-eared slider (<i>Trachemys scripta elegans</i>) exhibits seasonal variation, with enhanced sensitivity observed in spring compared to winter. However, the molecular mechanisms underlying these seasonal shifts remain unclear.</p> Results <p>Combined transcriptomic and metabolomic analyses revealed significant seasonal changes between sexes. Transcriptomic profiling identified pronounced organ-specific patterns, with the inner ear exhibiting the most profound seasonal reprogramming, as identified by Weighted Gene Co-expression Network Analysis (WGCNA), while the brain showed minimal changes. These changes primarily involved pathways associated with sensory transduction, neurotransmission, ion homeostasis, cytoskeletal organization, and intercellular communication. Key genes (including <i>GJB2</i>, <i>GJB6</i>, <i>OTOA</i>, and <i>OTOG</i>) showed marked differential expression between seasons. Metabolomic profiling further identified seasonal differences in carbohydrate metabolism, with elevated levels of oxaloacetic acid and succinic acid (TCA cycle intermediates) alongside propionic acid (a precursor feeding into the TCA cycle via propanoate metabolism) in spring, collectively suggesting intensified energy metabolism that may support enhanced auditory function.</p> Conclusions <p>These results provide molecular and metabolic insights into the seasonal plasticity of auditory sensitivity in red-eared sliders. The upregulation of key genes and metabolites related to energy metabolism and neural function during spring may facilitate improved auditory performance. This study enhances our understanding of the adaptive mechanisms underlying sensory plasticity in reptiles.</p>