Coffee became a beverage that was in demand in the world and consequently produced millions of tons of coffee byproducts namely coffee silverskin (CS). Unutilized CS will be waste and cause environmental pollution such as greenhouse gas emissions, landfill waste, and groundwater contamination. This is a research concern at this time, although many studies have been conducted to find newer applications of CS, exploration of its benefits in the health sector is still limited. Therefore, exploring the benefits of CS to prevent or delay aging will be very interesting to develop in functional food industry technology. Therefore, this study aims to report profiling metabolites or phytochemicals, biological activities in terms of antioxidant activity, and potential anti-aging of CS via molecular docking simulation and in vitro modulation of the mTOR/AMPK/SIRT1 pathway. Something new has been obtained from this work, the profile of phytocompounds, and biological activities both in molecular docking simulation and in vitro studies. Some of the compounds observed in Robusta CS extract (rCSE) such as Epicatechin, Kaempferol, and Quercitrin, and Arabica CS extract (aCSE) such as (+)-Catechin dan Naringin have promising potential as inhibitors of iNOS, mTOR, and HIF-1α via molecular docking simulation. Interestingly, the in vitro biological activity assay of antioxidant and anti-aging activity, rCSE showed the same promising potential as the results of a molecular docking simulation. More interestingly, AMPK/SIRT1/mTOR expressions are well modulated by rCSE compared to aCSE significantly (p < 0.05). This makes the rCSE have promising biological activity as a candidate for functional food development and/or treatment agent in combating free radicals that cause the aging process. In vivo studies and human trials are certainly needed to see the further efficacy of the rCSE in the future.