The fall armyworm Spodoptera frugiperda (J.E. Smith) is invasive pests in Egypt, and is considered the most important Lepidopteran pest to global agriculture. This study targeted studying the effect of different gamma radiation doses on S. frugiperda, and to evaluate its potential as a control measure. Five-day-old pupae received radiation treatments at dosages of 100, 200, 300 and 400 Gy. The results showed that irradiation with 100, 200, 300 and 400 Gy had no significant effect on male adult emergency (30%, 33%, 23% and 34%), however adult females were further susceptible than males that recorded 37.74%, 28.30%, 29% and 29.33%, respectively. Afterward irradiation with the substerilizing doses of 200 and 300 Gy, there was no egg hatchability. The results showed that, no significant difference among radiation doses of 100, 200 and 300 Gy in total protein and protease enzymes, while the high dose induced highly significant reduction in the activity of alkaline phosphatase and lactate dehydrogenase (LDH). Gamma radiation is hygienic, an efficient and secure physical restraint tool for controlling S. frugiperda, and it can reduce the pest population. It is also highly effective against enzymatic activity of target pests.