This chapter provides a methodological perspective on applying in-cell NMR to study nucleic acids, seeking insights into their structure, dynamics, and interactions within the human intracellular environment. It begins by outlining the experimental workflow, followed by detailed discussions on the preparation of DNA and RNA oligonucleotides. Design principles, synthesis, and purification methods are described, followed by the explanation of a cost-effective approach for obtaining isotopically labeled RNA oligonucleotides. Human cell lines used in in-cell NMR for nucleic acids are explained, including their characteristics. Delivery techniques are outlined, accompanied by assessments of delivery efficiency, cell viability, and intracellular localization. The essential role of the bioreactor system in maintaining a consistent cellular environment for stable in-cell NMR experiments is emphasized. We then describe instrumental prerequisites and underscore the utility of imino 1H signals for probing structures, dynamics, and interactions involving introduced nucleic acids within living human cells. The principles of structural analysis and measurements are explained. For the exploration of base-pair dynamics, theoretical aspects and measurements are detailed. Techniques involving both labeled and unlabeled oligonucleotides are described for investigating nucleic acid interactions. Additionally, we present illustrative analyses, including the structure of triplex DNA, dynamics of G-quadruplex DNA, and interactions involving an RNA aptamer with target molecules.