Glucocorticoid steroids (prednisone, deflazacort) decrease muscle inflammation and prolong ambulation in Duchenne muscular dystrophy (DMD) but are not used in other muscular dystrophies. Gene correction therapies are expected to elongate the life span of DMD patients, but will likely expand chronic exposure to steroids. Chronic daily glucocorticoids elicit untoward side effects, including obesity. Alternative steroid regimens have been proposed to maintain clinical benefits while reducing side effects. We previously showed that both once-daily and once-weekly 1mg/kg steroids improved dystrophic muscle resistance to injury across murine models of Duchenne (mdx) and limb-girdle dystrophies (Dysf-null, Sgcg-null). Here we asked how once-daily versus low dose, once-weekly glucocorticoids divergently affected function and energy balance in dystrophic muscle. In mdx muscle, once-weekly 1mg/kg prednisone promoted nutrient utilization and energy production, supporting insulin sensitivity and gain in strength. Conversely, once-daily 1mg/kg prednisone decreased mitochondrial function and induced insulin resistance. Importantly, benefits of once-weekly prednisone were recapitulated in Dysf-null and Sgcg-null mice. Intriguingly, the effects elicited by weekly regimens in dystrophic mouse muscle were maintained by diurnal injections but were blunted by nocturnal injections, indicating that time-of-day intake regulates glucocorticoid-driven effects. To assess translational relevance of these findings, we compared data and biomarkers from DMD patients under daily versus weekend steroids (cumulative doses, ~217 mg/week and ~235 mg/week, respectively), and found that weekend dosing reduced obesity and insulin resistance, with comparable effects on ambulation and heart function. Thus, low dose, weekly glucocorticoids can benefit muscle function and nutrient homeostasis across muscular dystrophies, and time-of-day of drug intake is an important variable for glucocorticoid effects.