Processing the coffee cherry into roasted beans generates a large amount of by-products, which can negatively impact the environment. The aim of this study was to analyze the bioactive potential and chemical composition of different coffee by-products (pulp, husk, parchment, silverskin, defective beans, and green coffee sieving residue) having in mind their bioactive potential for health and well-being. The coffee by-products showed a distinct nutritional composition. The content of ash, protein, fat, and total dietary fiber was significantly higher (p< 0.05) in coffee pulp (10.72% dw), silverskin (16.31% dw), defective beans (8.47% dw), and parchment (94.19% dw), respectively. Defective beans and the sieve residue exhibited a higher content of total phenolics (6.54 and 5.11 g chlorogenic acid eq./100 g dw, respectively) as well as higher DPPH•scavenging activity (3.11 and 2.85 g Trolox eq./100 g, respectively) and ferric-reducing antioxidant power (17.68 and 17.56 g ferrous sulfate eq./100 g dw, respectively). All the coffee by-products considered in this study are sources of caffeine and chlorogenic acids, in particular 5-caffeoylquinic acid (5.36–3787.58 mg/100 g dw, for parchment and defective beans, respectively). Thus, they can be recycled as functional ingredients for food, cosmetic and/or pharmaceutical industries, contributing to the social, economic, and environmental sustainability of the coffee industry.