Life-history traits such as growth, reproduction, and lifespan in animals are shaped by both genetic and environmental factors, with nutrition being one of the most important environmental factors. However, it remains unclear how and to what extent changes in the nutritional environment affect animals and what molecular mechanisms they employ to adapt to these varying conditions. In recent years, the fruit fly Drosophila melanogaster and related species have been developed as model systems for studying the effects of nutrition and microbes on animals at the molecular level. This review summarizes recent findings on nutritional adaptation in Drosophila species, focusing on nutrition-dependent neuronal developmental mechanisms, carbohydrate-responsive systems that generate differences in adaptabilities among species, and animal-associated microbes that support host growth.