Worldwide, around 10 million tons of coffee are consumed each year, producing almost as many tons of coffee by-products such as spent coffee grounds (SCG), the residue obtained after coffee brewing and soluble coffee production and coffee silverskin (CS), during the roasting process. Therefore, various applications have been proposed for SCG and CS valorisation, as they are a good source of nutrients and bioactive compounds such as soluble dietary fibre, protein, minerals, fat, caffeine and polyphenols[1]. They have been proposed as feedstock for biofuel production, adsorbent material to remove potential toxic metals in water, food products enrichment rather than for potential applications of theirs extracts as functional ingredient in cosmetic and nutraceutical formulations[2]. In our research group, the two matrix have been fully chemically characterize in terms of fat and fatty acid profile, volatiles by GC-O and GCXGC-TOF and, for the first time, cholesterol-lowering phytosterols were quantified in CS and SCG. Moreover, different ultrasound-assisted extraction (UAE) methods have been tested to extract bioactive compounds from CS and SCG. The obtained extracts were characterized using a new HPLC-MS/MS method to detect and quantify 30 bioactive compounds such as alkaloids and polyphenols, including phenolic acids, flavonoids, and secoiridoids. Four extracts, i.e. MeOH, EtOH/water 70:30, MeOH/ water 50:50 and water have been chosen among all because they provided high extraction yields, the effectiveness of compounds extraction, high recoveries other than the highest total bioactive compounds concentration. Finally, different biological studies were performed on these four extracts, and noteworthy results were obtained for the neuroprotective activity against H2O2-induced damage, for neuroinflammation and for enzymatic inhibitory activities.