NK cells are crucial for innate immunity and rapidly target abnormal cells through ligand-receptor signaling, without prior sensitization. Vitamin C is a bioenhancer of NK cells; however, its susceptibility to oxidation limits its efficacy in NK cell activation. This study evaluated the efficacy of Aptamin C, a stable conjugate of vitamin C and an aptamer, in enhancing NK cell activation. In in vivo study, 109 participants were ad-ministered either Aptamin C (36.057 mg/day) or placebo for 4 weeks. The results showed significant increases in NK cell cytotoxicity after 2 and 4 weeks in the Aptamin C group. Additionally, cytokine and granule levels associated with NK cell activity peaked in the serum 4 weeks after Aptamin C intake. In in vitro study, NK-92 cells treated with Aptamin C were compared to NK-92 cells treated with vitamin C. The results showed enhanced proliferation, survival, cytotoxicity, and cytotoxic granule production in NK-92 cells treated with Aptamin C compared to cells treated with vitamin C. These findings indicated that Aptamin C effectively promoted NK cell ac-tivation, suggesting its potential as an immunomodulatory supplement in NK cell therapy.