Aging is associated with a decline in motor function, which is a primary contributor to diminished functional capacity, increased risk of developing mobility limitations, and clinical disability. Multiple subdomains of motor function are reduced with aging including power, strength, balance, and endurance. Of these, declines in power, as assessed by leg‐extension power, occur earlier and more rapidly with aging. As such, leg‐extension power is one of the strongest predictors of overall physical performance and mobility in older adults. The exact mechanisms underlying age‐related changes in motor function are incompletely understood; however, excessive production of reactive oxygen species by mitochondria (mtROS) may play a role. Accordingly, preclinical data from our laboratory indicate that decreasing mtROS with the mitochondria‐targeted antioxidant MitoQ improves multiple subdomains of motor function in old mice (26–28 months). The purpose of the current study was to translate our preclinical findings to humans by conducting a randomized, placebo‐controlled, crossover clinical trial to assess the efficacy of 6 weeks of oral MitoQ (20 mg/day) vs. placebo supplementation for improving motor function (18 healthy late middle‐aged and older adults, 60–79 yrs). Leg‐extension power assessed at 40% of 1‐repetition maximum was 11% higher with MitoQ supplementation vs. placebo (860±63 vs. 803±71 W, P=0.02). Furthermore, there was an inverse relation between the improvement in leg‐extension power with MitoQ and leg‐extension power assessed under placebo conditions (r=−0.45, P=0.03). Leg strength, balance, endurance, and other subdomains of motor function assessed as part of the NIH toolbox motor battery were not different between conditions (all P>0.05). Aerobic exercise capacity (VO2max) and other participant characteristics were not altered with MitoQ (all P>0.05). Our data demonstrate that 6 weeks of supplementation with MitoQ in healthy late middle‐aged and older adults improves leg‐extension power, a critical determinant of mobility and physical function in this population. Moreover, our data suggest greater improvements in leg‐extension power with MitoQ supplementation in individuals with lower baseline function. Collectively, these data indicate that MitoQ and other therapeutic strategies targeting mtROS may hold promise for improving motor function and reducing the risk of clinical disability with aging.Support or Funding InformationSupported by NIH AG049451, AG053009, AG000279, and an industry contract with MitoQ Limited.