With breakthrough of cellulose pretreatment and enzyme hydrolysis technology, the fermentation process itself has become the main limiting factor for bio-ethanol manufacturing. Self-cycling fermentation (SCF) is an advanced configuration that could improve cell metabolic intensity, increase productivity and downsize substrate run-away. However, the modeling and monitoring techniques are in short that might hamper the realization of the SCF apparatus in industrial scale. In this work, a rigorous ethanol fermentation model considering the respiration effect of yeast S. cerevisiae is established; then, superiority and stability criterions under periodic load variations are developed for the SCF configuration; afterwards, repetitive control is proposed to stabilize the state trajectories related to SCF, the control laws include adaptive adjustment mechanisms for uncertainties of the input, nonlinear estimation of the unknown influential concentration through higher order sliding mode observer, and state observers and parameter estimators used to estimate the unknown states and kinetics. Since the temperature is an important factor for an efficient operation of the process, a split ranging control framework is also developed. As a conclusion, SCF demonstrates as a potential configuration when improvements in substrate conversion and productivity is pursued, but difficulty on proper monitoring of the triggering signals (for discharge-and-refill) might hamper its application, and the proposed feedback loops could be a solution to realize SCF under various scenarios.