Nmnat is a stress response protein which has been involved in a variety of biological processes. However, the effects of Nmnat on aging have not yet been investigated. The present study revealed the effects of Nmnat on aging of Drosophila and uncovered its underlying mechanism. Therefore, the overexpression of Nmnat was established by arm/Gal4 system in Drosophila with an aim to determine the functions of Nmnat during aging process. In this study, our results showed Nmnat was a positive factor on lifespan and movement capacity, which was consistent on d-galactose induced aging acceleration. Further investigation showed that oxidative stress biomarkers, longevity gene, mitochondria related genes and ATP levels were significantly improved in the Nmnat overexpression Drosophila, which suggested that the underlying mechanism of Nmnat on aging process and movement capacity was partly due to its anti-oxidative stress and mitochondrial-protection function. In addition, on H2O2 challenge tests, Nmnat overexpression was sufficient to increase the survival time and movement capacity of Drosophila, which was probably due to its protection against oxidative stress. On rotenone induced mitochondrial dysfunction, Nmnat overexpression also showed better health span and movement capacity than the control group. Based on these data, Nmnat may be a new molecular target to improve health span by enhancing stress resistance and locomotor activity in aging process.