As muscle function deteriorates with age, the discovery of new ways to enhance the quality of human life by stunting inevitable aging processes, such as sarcopenia, is a subject of great interest to aging populations, to health care professionals and to nutritional companies. β-hydroxy-β-methylbutyrate (HMB) enhances muscle strength in humans and attenuates disease-induced and disuse-dependent atrophy in rodents. We investigated the feasibility of utilizing Drosophila as a model organism to study the biological effects of HMB in aging muscle. Using flight ability as an index of muscle function and monitoring the lifespan of flies, we found that normal food supplemented with 10 mg/mL HMB, supplied from eclosion through adulthood, attenuates the age-dependent decline in flight ability and enhances longevity of flies. To further discern the dietary optimization of HMB supplementation, we examined the effect of 10 mg/mL HMB supplementation from the larval stages throughout adulthood under various dietary conditions. As dietary restriction without malnutrition and HMB supplementation independently increase longevity in flies, we investigated the relationship between dietary restriction and HMB supplementation. Flies were subject to non-restricted, reduced yeast (protein), or intermittently cycled feeding regimens, with or without HMB. Both modes of dietary restriction improved flight ability, while only cycling flies on and off food increased lifespan and improved survivorship of the flies. HMB supplementation increased flight ability later in life in all groups, but had differential effects on lifespan; HMB improved the survivorship of females fed a reduced yeast diet, but decreased the survivorship of both non-restricted and intermittently fed flies. This not only suggests that HMB may act via different pathways to influence fly flight and survivorship, but that these mechanisms may differ under various dietary conditions, in different sexes. Because HMB supplemented dietary restriction had different effects on flight ability and survival than dietary restriction alone, HMB likely acts via different mechanisms than dietary restriction. Sex specific effects were found, suggesting that future HMB and dietary restriction studies should make distinctions between effects in males and females. As the flight ability and longevity of D. melanogaster was affected by HMB supplementation under various dietary conditions, future studies may use D. melanogaster as a model organism to explore the effects of HMB on age-related muscle deterioration and to help uncover the biological mechanisms of such observations, as well as potential treatments for age-associated muscle dysfunction and disease.