Since the problem of the Food Waste has become a global concern, this study has the goal to make full use of the Zero-Waste concept, which is the ideal approach to find a way to recycle all the parts of any kind of food product, without producing waste. To the aim, prickly pears (Opuntia ficus indica) were completely used as pulp and as by-products to produce an active powder to be added as ingredient in fish burgers. As a fact, prickly pears are tropical plants, rich in polyphenolic compounds, able to control microbial proliferation and general detrimental phenomena occurring in food. For the current study, the pulp and the peel were separately dehydrated and reduced to a fine powder in order to be used as food ingredients in cod fish burgers to prevent microbial growth and improve sensory quality during storage at 4 °C. An in vitro test of the sole powders was also carried out against target microorganisms. After that, three different concentrations (i.e., 2.5 g, 7.5 g and 12.5 g) of peel and pulp in proper combination (for 1 g of prickly pear powder, 0.57 g of pulp and 0.43 g of peel) were added to fish burger formulation. Results demonstrated that prickly pear powder has an important antimicrobial activity. Its addition to fish formulation improved microbial quality of burgers, reducing the growth of main fish spoilage microorganisms (i.e., Pseudomonas spp.,psychrotolerant and heat-labile aerobic bacteria and psychrotropic bacteria) and that 12.5 g was the best amount to be used. The prickly pear powder added to fish also contributed to control the sensory quality decay during storage.