Coffee silverskin (CS) is the only byproduct of the roasting process for coffee beans and is rich in phenolic compounds with various bioactivities. This study proposes a valorization option for bioactive compounds (T-CQA) based on a subcritical water extraction (SWE) technique, which is known for its high efficiency and feasibility for use on an industrial scale. The use of water as a sole solvent requires a minimum number of cleaning steps and renders the extract safe for further applications, such as in either the cosmetic or food industry. Response surface methodology with a Box–Behnken design is effectively used to optimize and explain the individual and interactive process variables (i.e., extraction temperature, extraction time, and solid–liquid ratio) on the T-CQA content obtained from coffee silverskin by the SWE technique. The final model exhibits a precise prediction of the experimental data obtained for the maximum T-CQA content. Under the optimum conditions, the CS extract is found to contain a higher content of T-CQA and TPC than that reported previously. For antioxidant activity, up to 26.12 ± 3.27 mg Trolox equivalent/g CS is obtained.