Electrochemical DNA sensors offer high sensitivity, selectivity, and low cost for detecting DNA sequences or mutated genes associated with human disease. These sensors utilize nanoscale interactions between the target DNA, recognition layer, and electrode surface. Various methods include direct DNA electrochemistry, polymer-modified electrodes, redox reporters, nanoparticle-based amplification, and DNA-mediated charge transport. Over the past 15 years, significant advances have enabled the development of biosensors for monitoring biorecognition events on solid devices and in solution. Gene chips with dense oligonucleotide arrays have been used for transcriptional profiling and SNP discovery, but their fluorescence-based readout is expensive and complex. Recent innovations in DNA-based electrochemical sensing combine nucleic acid layers with electrochemical transducers to create biosensors that are simple, accurate, and inexpensive for patient diagnosis. Optical readout methods include gene chips, SPR, and colorimetric assays using gold nanoparticles. These methods offer high sensitivity but require sophisticated instrumentation. Mass-based readout methods like QCM and microcantilevers detect mass changes upon target binding, though they face challenges in fabrication and instrumentation. Electrochemical readout is well-suited for DNA diagnostics due to its direct electronic signal and low cost. Techniques such as direct DNA oxidation, indirect electrochemistry using mediators, and DNA-specific redox indicators have been developed. These methods include sandwich assays, enzymatic amplification, and DNA-mediated charge transport, which provide high sensitivity and specificity for detecting mutations and protein-DNA interactions. DNA-based electrochemical sensors have been applied to detect proteins and small molecules that bind to DNA. These sensors leverage the structural uniformity of DNA for reliable electrode surface assembly. Challenges remain in scaling up sensor arrays for clinical applications and improving the sensitivity and specificity of DNA detection. Despite these challenges, electrochemical DNA sensors offer promising tools for disease diagnosis and environmental monitoring. Their low cost, small size, and inherent sensitivity make them valuable for clinical and point-of-care diagnostics.Electrochemical DNA sensors offer high sensitivity, selectivity, and low cost for detecting DNA sequences or mutated genes associated with human disease. These sensors utilize nanoscale interactions between the target DNA, recognition layer, and electrode surface. Various methods include direct DNA electrochemistry, polymer-modified electrodes, redox reporters, nanoparticle-based amplification, and DNA-mediated charge transport. Over the past 15 years, significant advances have enabled the development of biosensors for monitoring biorecognition events on solid devices and in solution. Gene chips with dense oligonucleotide arrays have been used for transcriptional profiling and SNP discovery, but their fluorescence-based readout is expensive and complex. Recent innovations in DNA-based electrochemical sensing combine nucleic acid layers with electrochemical transducers to create biosensors that are simple, accurate, and inexpensive for patient diagnosis. Optical readout methods include gene chips, SPR, and colorimetric assays using gold nanoparticles. These methods offer high sensitivity but require sophisticated instrumentation. Mass-based readout methods like QCM and microcantilevers detect mass changes upon target binding, though they face challenges in fabrication and instrumentation. Electrochemical readout is well-suited for DNA diagnostics due to its direct electronic signal and low cost. Techniques such as direct DNA oxidation, indirect electrochemistry using mediators, and DNA-specific redox indicators have been developed. These methods include sandwich assays, enzymatic amplification, and DNA-mediated charge transport, which provide high sensitivity and specificity for detecting mutations and protein-DNA interactions. DNA-based electrochemical sensors have been applied to detect proteins and small molecules that bind to DNA. These sensors leverage the structural uniformity of DNA for reliable electrode surface assembly. Challenges remain in scaling up sensor arrays for clinical applications and improving the sensitivity and specificity of DNA detection. Despite these challenges, electrochemical DNA sensors offer promising tools for disease diagnosis and environmental monitoring. Their low cost, small size, and inherent sensitivity make them valuable for clinical and point-of-care diagnostics.