Background: Scorpion envenomation is a common hazard in many parts of the world and in Sinai, hence great attention must be directed towards such animals to avoid or reduce their dangers. One of the most common antioxidant medicinal plants in Sinai is the Ambrosia maritima or Damsisa plant; it is playing an important rolein reducing or neutralizing the toxic effects of venoms. Also, the Allium sativum plant or (garlic) has been used for many years to treat a variety of medical problems. Aim of work: the present study was prepared to illustrate the protective effect of damsisa and garlic plant extracts in different tissues of mice envenomed with Leiurus quinquestriatus scorpion venom. Materials and methods: 48 albino mice were divided into 6 groups. Group I: the healthy control rats received tap water for 4 weeks, and then intramuscularly (i.m.) injected with saline solution and sacrificed after 48 hours from an injection. Group II: envenomed mice were intramuscularly injected with (0.15 µg/g b.wt.) dose of the scorpion venom and sacrificed after 48 hours from envenoming.  Group III: mice treated with a daily oral dose of Damsisa plant extract (100 mg/kg) for 4 weeks; Group IV was treated with a daily oral dose of garlic plant extract (220 mg/kg) for 4 weeks. Group V: the envenomed mice were injected with the same dose of the scorpion venom and pretreated with oral doses of Damsisa (100 mg/kg b. wt) for 4 weeks. Group VI: the envenomed mice were injected with the same dose of the scorpion venom and pretreated with an oral dose of garlic plant extract (220 mg/kg b. wt) for 4 weeks. All mice were sacrificed after 48 hours from envenoming. At the end of the experiment, some tissues samples from skeletal muscles, testis, and lung tissues were collected for histopathological, immunohistochemical, and DNA ladder assay. Results: envenomed mice had severe cellular degeneration, cytoplasmic vacuolization, cellular infiltrations, and marked dilatation of blood vessels in the skeletal muscles, testis, and lung tissues. This result is confirmed with extreme immunohistochemical changes in lung tissues and the results of the DNA ladder assay revealed increased DNA fragmentation in brain tissues. The envenomed and plant-treated mice revealed marked diminished effects in histopathological alternations in the studied tissues compared to envenomed mice and reduced DNA fragmentation in brain tissues. Conclusion: This study concluded that Ambrosia maritima (D) and Allium sativum (G) plants have a protective effect against scorpion envenomation and especially the garlic plant showed the best results. Our results suggested that the ameliorative effects of these plant extracts may be due to the antioxidant and anti-inflammatory properties of these plants in combating free radical-induced oxidative stress and tissue injury resulting from envenomation.