Abstract: In this work, three types of electrochemical sensors, namely E-DNA, E-Ion and E-Drug, were designed and fabricated for the analysis of DNA, metal ions and anticancer drugs. Chapter 1 describes a brief introduction. The background of analytes of interest and the electrochemical techniques used for sensor characterization are introduced. The effects of DNA probe and target flexibility on the performance of a “signal-on” electrochemical DNA sensor is detailed in Chapter 2. Chapter 3 describes differentiating flexibility of four nucleotides (adenine (A), guanine (G), cytosine (C) and thymine (T)) based on electrocatalytic reactions between the redox label methylene blue (MB) attached on the oligonucleotides and the electrochemical species ferricyanide (Fe(CN)63- ) and platinum (IV) ion (Pt4+). Chapter 4 demonstrates two electrochemical DNA sensors based on electrostatically assisted surface assembly of gold nanostars (AuNs). Both the redox labeled stem-loop probe (SLP) and linear probe (LP)-based electrochemical DNA (E-DNA) sensors fabricated on the AuNs were systematically characterized. Chapter 5 displays an electrochemical gold (III) sensor with a high sensitivity and tunable dynamic range. DNA probes with consecutive adenines were used in this study. Chapter 6 continues the study on the effect of DNA probe length on the dynamic range and limit of detection of electrochemical ion sensors. Three thiolated oligothymine probes and three thiolated oligoadenine probes were fabricated for the detection of Hg(II) and Au(III), respectively. Chapter 7 presents DNA-based electrochemical ion (E-ION) sensors for the detection of Ag(I). The effect of the probe sequence, as well as the location of the alkanethiol linker and MB redox label, on the overall performance of the sensors were evaluated. Chapter 8 focuses on a “signal-on” cisplatin sensor. The intra-strand crosslinks generated between the aquated cisplatin and the AG-rich probe induced a kink on the probe and dominated the “signal-on” behavior at high ACV frequency such as 200 Hz. A “signal-on” electrochemical sensor for detection of satraplatin (SAT) is described in Chapter 9. The detection strategy is based on the electrocatalytic reaction between the Pt(IV) center of SAT and the surface-immobilized MB. Chapter 10 concludes this dissertation. Future direction of this study is also planned.