The use of natural antimicrobials in the food industry is being proposed as an eco-friendly postharvest technology to preserve fruit-derived foods. In this context, this systematic review aims to describe and discuss the application of naturally occurring antimicrobial compounds in the processing of fruit-derived foods by the PRISMA methodology. In a first step, the use of free natural antimicrobials was investigated as an approach to identify the main families of bioactive compounds employed as food preservatives and the current limitations of this dosage form. Then, the use of immobilized antimicrobials, in an innovative dosage form, was studied by distinguishing two main applications: addition to the food matrix as preservatives or use during processing as technological aids. Having identified the different examples of the immobilization of natural antimicrobial compounds on food-grade supports, the mechanisms of immobilization were studied in detail to provide synthesis and characterization guidelines for future developments. Finally, the contribution of this new technology to decarbonization and energy efficiency of the fruit-derived processing sector and circular economy is discussed in this review.