Origanum majorana (OM) is known to have antioxidant properties. The present work was designed to evaluate, for the first time, the hepato/nephroprotective, immunomudulatory and antibacterial potentials of OM leaves acetone extract (OMLE). OML was collected from Al-Soudah, Aseer, Saudi Arabia, and OMLE was prepared. Active biomolecules were screened utilizing FT-IR spectroscopy, protein electrophoresis and HPLC. Reactive oxygen species (ROS) were measured using ELISA. Male rats were treated with OMLE and livers, kidneys and sera were collected. Liver enzymes, kidney function markers, antioxidants in liver and kidney tissues and tumor markers were quantitated. OMLE immunomodulatory potentials were tested using rat splenocytes. Antimicrobial power was tested against Gram negative/positive bacteria. The extract contained many functional biomolecules and ROS but no sugars and proteins. OMLE treatment did not affect liver and kidney functions or the tumor markers. There were some changes in measured antioxidant biomolecules. The extract is not harmful to hepatocytes as indicated by levels of AST and ALT. It is not carcinogenic as it did not make any changes in tumor marker levels. The extract could modulate the splenocytes. The use of OMLE is useful in protecting normal vital organs from oxidative stress. It can also be used as immunostimulant.