To address the metabolic instability of cordycepin induced by adenosine deaminase (ADA) and to enhance its bioactivity, this study developed eleven novel cordycepin derivatives using molecular engineering techniques. By incorporating sterically hindered protective groups and modifying the glycosyl moiety, the research aimed to improve both stability and efficacy. Antibacterial tests revealed that five derivatives showed significantly greater activity against pathogenic strains compared to cordycepin, with better compatibility with probiotics. Compound 2 c demonstrated moderate antitumor activity against K562 and MGC-803 cells, with IC