Alzheimer’s disease (AD) is the neurodegenerative condition with the outmost future challenges, with timely diagnosis and treatment being the most urgent. Discovery of more and more biomarkers is widely attempted; however, current diagnostic methods often lack sensitivity, specificity, and accessibility. Nucleotide aptamers—short, highly specific oligonucleotide or ligands—are now recognized as highly promising molecular agents for both measuring and targeting key AD biomarkers, with the most notorious being amyloid-beta (Aβ), tau protein, and disease-associated microRNAs (miRNAs). This review provides a comprehensive analysis of nucleotide aptamers related to AD, detailing their mechanisms of selection, recent advances in biosensing applications, and therapeutic potential. Aptamers, targeting the most significant biomarkers of AD, are mainly discussed, as well as ones interacting with novel, promising biomarkers, with a special aim on miRNAs. Additionally, aptamers are compared with conventional antibody-based approaches, highlighting their advantages in terms of stability, cost-effectiveness, and ease of modification. By elucidating the role of aptamers in AD diagnosis and treatment, this review underscores their promise as next-generation tools for precision medicine and neurodegenerative disease management.