Food-waste is produced throughout all the food supply chain, with a large part already achieved at farm level. In fact, fruits and vegetables, which do not satisfy aesthetic demands, cannot be marketed, but their recovery could favour their valorisation for the obtainment of highly qualified goods. In this context, faulty zucchini fruits (cultivar ‘Lungo Fiorentino’), intended for disposal, were rescued as effective, inexpensive and bio-sustainable source for cosmeceutical purposes. Zucchini fruits underwent extraction and fractionation to obtain ZLF-O and ZLF-A extracts, which were chemically characterized by UHPLC-HRMS. ZLF-A extract, rich in flavonols and flavones, scavenged massively DPPH• and ABTS•+, and was not cytotoxic at doses up to 200 μ g/mL. Thus, ZLF-A was incorporated into a base cream formula. Zucchini-based emulsion was deeply screened for its antiradical properties and cytotoxicity towards human keratinocytes and fibroblasts. ZLF-A-enriched cream, whose chemical stability was assessed over time and mimicking different storage conditions, was further tested on reconstructed epidermis disks (EpiskinTM). The recovery of valuable chemical substances from zucchini agro-food waste, complying with the principles of valorisation and sustainable development, can represent a new market force for local farmers. Data acquired were eager to convey a suitable reuse of nutraceuticals rich zucchini waste.