Background <p>Oysters are known for their rich nutritional profile and medicinal properties documented in traditional medicine. Their bioactive compounds exhibit antioxidant, anti-inflammatory, antimicrobial, and osteogenic activities, leading to widespread applications in food and medicine. Oyster shells—composed of &gt; 90% calcium carbonate and various minerals and amino acids—are traditionally used as antacids in East Asia. Despite these recognized benefits, the mechanisms by which oyster shells modulate immune responses remain unclear. In this study, we elucidated the immunomodulatory effects of Ostreae Testa water (OTW) extract from oyster shells, focusing on OTW’s ability to modulate T cell responses.</p> Methods <p>Mouse splenocytes were treated with OTW extract, and T cell activation was assessed. The role of antigen-presenting cells (APCs), including dendritic cells (DCs) and macrophages, was assessed by analyzing cytokine profiles and cell-cell interactions. OTW extract-primed CD8⁺ T cells were assessed for anti-tumor responses in an in vivo solid tumor model.</p> Results <p>OTW extract treatment significantly enhanced T cell activation in mouse splenocytes. DCs and macrophages mediated this effect, facilitating the immune response via cytokine and direct interactions with T cells. Moreover, OTW extract-primed CD8⁺ T cells enhanced anti-tumor immune responses in the solid tumor model, demonstrating potent immunotherapeutic potential.</p> Conclusions <p>Our findings demonstrate that OTW extract exhibits novel immune-enhancing properties by activating APCs and subsequently promoting T cell responses. These results underscore the therapeutic potential of OTW extract for improving immune function, particularly in the context of immunological disorders and cancer.</p>