Coffee consumption continues to grow all over the world and in 2019 the equivalent of 167.90 million 60-kg bags were consumed worldwide, with Brazil being the largest producer and exporter and the second largest consumer of the beverage. The amount of coffee by-products generated is extremely high, being mainly composed of immature/defective coffee, coffee husks, silver skin and spend coffee grounds (SCG). Studies indicate that SCG oil contains high concentrations of polyunsaturated fatty acids, primarily linoleic and palmitic acids, which have excellent skin emollient and moisturizing properties. This paper reports an analysis of the degree of toxicity, collagen synthesis and the potential for proliferation and cell migration of SCG oil after passing through a pre-extraction process with innovative non-thermal plasma (NTP) technology. It was found that coffee oil subjected to NTP has low toxicity and great potential for cell proliferation and migration compared to oil extracted without NTP treatment. This will be of great interest to the pharmaceutical and cosmetic industries, adding value to a waste product available in large quantities in association with the use of a clean technology (non-thermal plasma).