Food companies should comply with the requirements of a zero‐waste concept to adapt to the circular economy requirements. In fruit companies, usually seeds are discarded without proper utilization and extraction of the bioactive compounds. Fruit seeds are sources of chemical compounds that can be extracted, studied, and applied in high value‐added products. Thus, in this work the experimental conditions for the water extraction of phenolic compounds from camu‐camu (Myrciaria dubia) seed coat were optimized using a central composite design and the desirability function. Total phenolic content (TPC), and condensed tannins (CT), DPPH radical scavenging activity, ferric reducing antioxidant capacity (FRAP), Folin‐Ciocalteu reducing capacity (FCRC), and Cu2+chelating ability were assessed. Seed coat extracted for 51.1 min using a 1:34.1 solid:liquid ratio was the optimal condition to extract 6,242 mg gallic acid equivalent (GAE)/100 g of TPC and 695 mg catechin equivalent (CE)/100 g of CT. The optimized extract displayed free‐radical scavenging activity, reducing properties and ability to chelate Cu2+, and inhibited the growth of Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella Typhimurium, Salmonella Enteritidis, Bacillus cereus, and Staphylococcus aureus. Additionally, the lyophilized water extract inhibited the in vitro activity of α‐amylase, α‐glucosidase, and angiotensin converting enzyme and showed cytotoxic effects towards Caco‐2, A549, and HepG2 cancer cells, but no cytotoxicity towards IMR90 cells. Vescalagin, castalagin, and 3,4‐dihydroxybenzoic acid were the major phenolic compounds identified in the optimized extract. In conclusion, the optimized camu‐camu seed coat water extract is a rich source of phenolic compounds with antioxidant, antidiabetic, antihypertensive, and antiproliferative effects. Practical Application Camu‐camu fruit pulp and seeds have been studied for their phenolic composition and bioactivity. However, seeds are usually discarded and represent an environmental problem in South American countries. We presented a methodological overview on the extraction optimization of the phenolic compounds from camu‐camu seed coat and studied the bioactivity of the optimized extract using chemical, enzymatic, and cell‐based experiments. Results can be used by camu‐camu processors to obtain a phenolic‐rich extract for industrial applications, without any further processing.