Industrial wastewater effluents containing dyes are considered to pollute and be harmful to the environment. Among the various removal techniques, the adsorption process using low-cost adsorbents has been successfully used to remove pollutants. In this work, Aloe vera leaves (AVs) have been used as adsorbent for the removal of Orange II (O-II). A three-level three-factor Box–Behnken factorial design, including three replicates of center points, was applied to investigate the main parameters affecting the biosorption of O-II dye in aqueous solutions by AVs. The selected parameters were adsorbent dose, initial dye concentration, and contact time. The Box–Behnken experiment design has given a satisfactory result for the optimization of the adsorption process. The obtained value of Rsup.2 (0.9993) shows that the quadratic response model adequately represents the relationship between each response and the chosen variables. The pH influences the adsorption capacity, obtaining at pH 2 the maximum adsorption capacity value. From the kinetic models studied, the one that best describes the adsorption of Orange II on Aloe vera is the Bangham model (ARE = 1.06%). The isotherm model that best represents the experimental data is the Toth model. The maximum adsorption capacity obtained by this model was 15.9 mg·gsup.−1.