The Mediterranean fruit fly Ceratitis capitata (medfly) is a major pest throughout the world and one of the most destructive. Several strategies for controlling this pest have been proposed, including the sterile insect technique (SIT). The SIT’s effectiveness against the medfly is well documented. Sterile medflies, on the other hand, can perform poorly. Reduced mating compatibility and mating competitiveness in the field may be caused by genetic and symbiotic differences between natural and laboratory medfly populations. Probiotic gut symbionts have been shown to facilitate control strategies and improve male medfly fitness. They are equally effective in the live and inactivated forms when administered to medfly adults or larvae. They have been shown to modulate a large set of inducible effector molecules including antimicrobial peptides (AMP) and stress-responsive proteins. The selection procedures of probiotics for their use in the medfly rearing process are reviewed, and other pathways for selection are proposed based on recent in silico studies. This chapter summarizes the most relevant evidence from scientific literature regarding potential applications of probiotics in medfly as an innovative tool for biocontrol, while also shedding light on the spectrum of symbiotic relationships in medfly that may serve as a powerful symbiotic integrative control approach.