Advances in microfabrication technology and miniaturized analysis have led to the development of lab-on-a-chip (LOC) systems, which enables integration of multiple complex functions on a single device. With the reduction in size to the micrometer or nanometer scale, LOC devices to minimize consumption of reagents, increase automation, and reduce manufacturing costs. Electrochemical and optical detection are popular techniques that are compatible with LOC devices for chemical and biochemical analysis. Scalability of electrochemical and optical detection schemes to smaller dimension enables the development of portable sensors with low background and enhanced sensitivity based on LOC devices.This work demonstrates the design and fabrication of several specific LOC devices for different applications by integrating electrochemical and optical detection. An electrochemical reactor was developed for in situ generation and quantitative monitoring of oxygen within nanofluidic systems. In this device, an embedded microband electrode was employed for reagent generation, and fluorescein, a pH-sensitive dye, was used as a reporter for monitoring the spatiotemporal distribution of generated O2 based on the co-produced H+. Importantly, the optical and electrochemical measurements were in quantitative agreement on total generation, whereas the fluorescence images allowed spatial/temporal maps of O2 to be generated. In the second application, bipolar electrode (BPE)-based LOC devices with physically isolated analytical and reporting regions were developed. Microchannels equipped with interdigitated array (IDA) electrodes were designed to couple independent electrochemical reactions (in an analytical cell) to fluorescence response (in a separate reporter cell) using a closed BPE geometry. Proton-coupled electron transfer reactions were investigated in the structure with integrated electrochemical pH modulation. In the third applications, a dual-cell electrochromic detector was developed in order to provide a simple detection method for electrochemical sensing. In this application, the colorimetric (electrochromic) indicator methyl viologen was coupled through a closed BPE to an analytical reaction in a separate cell. A smartphone was used to collect colorimetry data and provide a simple, fast, and reliable detection method with strong the potential for point-of-care and real-time diagnosis applications. Finally, these electrochromic devices were employed for the detection of common metabolites detection, such as glucose, lactate, and uric acid. By integrating multiple BPE components onto the same device, it was possible to detect multiple analytes and determine their concentrations simultaneously using colorimetry. Selectivity and sensitivity of the detection were further improved by introducing enzymes specific for target analytes and optimizing the reporter cell size. Work in this thesis establishes that closed BPE devices can be coupled with electrochemical and optical detection to provide new opportunities for simple, rapid, and effective detection.