Conventional methods of food preservation have demonstrated several disadvantages and limitations in the efficiency of the microbial load reduction and maintain food quality. Hence, non-thermal preservation technologies (NTPT) and alternative chemical compounds (ACC) have been considered a high promissory replacer to decontamination, increasing the shelf life and promoting low levels of physicochemical, nutritional and sensorial alterations of meat and fish products. The combination of these methods can be a potential alternative to the food industry. This review deals with the most critical aspects of the mechanisms of action under microbial, physicochemical, nutritional and sensorial parameters and the efficiency of the different NTPT (ultrasound, high pressure processing, gamma irradiation and UV-C radiation) and ACC (peracetic acid, bacteriocins, nanoparticles and essential oils) applied in meat and fish products. The NTPT and ACC present a high capacity of microorganisms inactivation, ensuring low alterations level in the matrix and high reduction of environmental impact. However, the application conditions of the different methods as exposition time, energy intensity and concentration thresholds of chemical compounds need to be specifically established and continuously improved for each matrix type to reduce to the maximum the physicochemical, nutritional and sensorial changes. In addition, the combination of the methods (hurdle concept) may be an alternative to enhance the matrix decontamination. In this way, undesirable changes in meat and fish products can be further reduced without a decrease in the efficiency of the decontamination.