Microplastics (MPs) have become a prominent environmental concern due to their ubiquity in various ecosystems and widespread distribution through multiple channels. In this study, the oral effects of 2,000 mesh polytetrafluoroethylene (PTFE) microplastics were tested against Drosophila melanogaster (Meigen), at concentrations of 0, 0.1, 1, 10, and 20. After exposure to a microplastic-containing medium for 20 days, energy metabolism, fecundity, spontaneous movement, and sleeping time were measured. The study results showed that glucose levels in male flies were significantly reduced after exposure to PTFE-MPs. Measurement of lipid and protein levels indicated an increase in males but decrease in females, whereas these changes were not statistically significant. Reduction in sleep time was also observed, especially in males at the concentration of 20 g/l. Our study indicates that chronic exposure of PTFE-MPs can change energy metabolism and the amount of sleep on D. melanogaster in a sex dependent and dose dependent way. The results of our study are hoped to contribute to a better understanding of the effects of microplastics as new pollutants on insects.