Orange peel, which is a by-product of oranges, contains carbohydrates that can be converted into sugars and used in the fermentation process. In this study, the thermal alkaline pretreatment process was chosen because of its simplicity and lesser reaction time. In addition, the reaction factors were optimized using response surface methodology. The determined optimal conditions were as follows: 60.1 g/L orange peels loading, 3% KOH and 30 min. Under the optimal conditions, glucan content (GC) and enzymatic digestibility (ED) were found to be 32.8% and 87.8%, respectively. Enzymatic hydrolysis was performed with pretreated and non-pretreated orange peels using three types of enzyme complex (cellulase, cellobiase and xylanase). The minimum concentrations of enzyme complex required to obtain maximum ED were 30 FPU (filter paper unit), 15 CBU (cellobiase unit), and 30 XNU (xylanase unit) based on 1 g-biomass. Additionally, ED of the treated group was approximately 3.7-fold higher than that of the control group. In conclusion, the use of orange peel as a feedstock for biorefinery can be a strategic solution to reduce wastage of resources and produce sustainable bioproducts.