The microscopic precision in simultaneous delivery of light and fluids by optofluidics offers great potential for global sustainability and health applications. Light drives photocatalytic reactions in a gas/liquid environment containing catalyst nanoparticles and reactants in global sustainability applications. The relevant efforts in this dissertation include: (1) a “shell-and-tube” glass waveguide-based photoreactor technology for converting CO2 to fuels, (2) a “gradient etching” approach to enable uniform light scattering of waveguides for enhanced photocatalytic degradation of methylene blue dyes, and (3) the optimization of both design and operating parameters of waveguide-based photoreactors via Multiphysics simulations. In global health applications, the fluidic environment involves various bodily fluids, such as serum, plasma, or human whole blood samples. Light irradiation by the optical reader excites the signals on test and control lines, and these line intensities are collected for later quantification of analyte concentrations. The health-related efforts in this dissertation include: (1) an iPad-based multiplexed lateral flow assay (LFA) system to differentially detect human malaria species with a single test line, (2) an optical reader-based multiplexed LFA system for differential diagnosis of malaria and typhoid infections, and (3) a fluorescence reader-based multiplexed LFA system for differentiating bacterial and viral infections.