Electrochemical methodology has probably been the most used sensing platform in the past few years as they provide superior advantages. In particular, screen-printed electrode (SPE)-based sensing applications stand out as they provide extraordinary miniaturized but robust and user-friendly detection system. In this context, we are focusing on the modification of SPE with functional nucleic acid probes and nanostructures to improve the electrochemical detection performance in versatile sensing applications, particularly in the fight against the COVID-19 pandemic. Aptamers are immobilized on the electrode surface to detect non-nucleic acid targets and complementary probes to recognize and capture nucleic acid targets. In a step further, SPE-based biosensors with the modification of self-assembled DNA nanostructures are emphasized as they offer great potential for the interface engineering of the electrode surface and promote the excellent performance of various interface reactions. By equipping with a portable potentiostat and a smartphone monitoring device, the realization of this SPE-based miniaturized diagnostic system for the further requirement of fast and POC detection is revealed. Finally, more novel and excellent works are previewed and future perspectives in this field are mentioned.