Many of the Jatropha species have found applications in folk medicine. This study aimed to evaluate the biological activity of Jatropha pelargoniifolia and Jatropha glauca total alcoholic extracts for root and aerial parts Euphorbiaceae family indigenous on the Arabian peninsula. J. glauca and J. pelargoniifolia, Euphorbiaceae, were collected in September 2015 from Wadi Shogare and Wadi Mojasas, respectivelly in Jazan south area of Kingdom of Saudi Arabia. In vivo and in vitro studies for their possible effects as hepatoprotective, antinociceptive, anti-inflammatory and antidiabetic/hypoglycemic medicinal herbal drug in comparison with standard clinical drugs. Hepatoprotective was assessed via serum biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT) and total bilirubin. Tissue parameters such as malonaldehyde (MDA), non-protein sulfhydryl groups (NP-SH) and total protein (TP) were also measured. Antinociceptive activity was explored by using hot plate and writhing methods. In addition, the anti-inflammatory effect was evaluated by using carrageenan-induced paw edema. Finally, hypoglycemic and antidiabetic activities in alloxan induced diabetic mice were evaluated for both Jatropha plants root and aerial parts. In conclusion: The root of J. glauca showed significant hepatoprotective and antinociceptive activities. The J. pelargoniifolia root revealed higher anti-inflammatory effect and hypoglycemic activity. Finally, J. glauca aerial part achieved significant antidiabetic activity in alloxan induced diabetes compared with glibenclamide.