The present work aimed to investigate and optimize the selective exploitation of hemicellulose and cellulose fractions of the energy crop Arundo donax L. (giant reed), to give xylose and levulinic acid, respectively. In order to improve the sustainability of this process, a microwave-assisted hydrolysis in the presence of FeCl was implemented using as substrate the raw biomass without any pretreatment process. The effects of the hydrolysis reaction conditions, such as temperature, reaction time, salt amount and biomass loading, on giant reed exploitation were investigated. In the first step, under the optimized conditions (150 °C, 2.5 min and 1.6 wt% FeCl), the xylose yield reached 98.2 mol%. In the second step, under the best conditions (190 °C, 30 min and 2.4 wt% FeCl), the levulinic acid yield was 57.6 mol%. This novel cascade approach ensured an extensive exploitation of giant reed polysaccharides working in the respect of Green Chemistry principles.