The medfly Ceratitis capitata is one of the most damaging fruit pests with quarantine significance due to its extremely wide host range. The use of entomopathogenic fungi constitutes a promising approach with potential applications in integrated pest management. Furthermore, developing insect control methods can involve the use of fungal machinery to cause metabolic disruption, which may increase its effectiveness by impairing insect development. Insect species, including C . capitata , relies on reproduction potential, nutrient reserves, metabolic activities, and immune response for survival. Accordingly, the purpose of this study was to investigate the impacts of the entomopathogenic fungus Purpureocillium lilacinum on C . capitata pre-mortality. The medfly V8 strain was subjected to laboratory bioassays, which consisted on determining the virulence of P . lilacinum on the medfly. Purpureocillium lilacinum was applied on abdominal topical of 5-day-old males and females. Following the fungal inoculation, we have confirmed (i) a significant increase in tissue sugar content, (ii) a significant decrease in carbohydrase activities, digestive glycosyl hydrolase, and proteinase activities in whole midguts of treated flies, (iii) the antimicrobial peptides (AMPs) genes expression profile was significantly influenced by fly gender, fly status (virgin, mature, and mated), and time after infection, but infection itself had no discernible impact on the AMPs for the genes that were examined. This study provides the first insight into how P . lilacinum could affect C . capitata physiological mechanisms and provides the foundation for considering P . lilacinum as a novel, promising biocontrol agent.