Gentamicin is an antibiotic widely used in treating bacterial infections. However, it's clinical interest is limited by it's toxic side effects on vital organs. Sarcophyton soft coral is a source of natural products with a range of bioactivities. As such, the objective of this work was to assess how well Sarcophyton extract mitigated the gentamicin toxicity in rats. Four equal groups, each with five adult male albino rats, were randomly assigned: the control group, the Sarcophyton group given a Sarcophyton extract dose of 200 mg/kg/day orally for seven days, the gentamicin group receiving an intraperitoneal gentamicin dose of 100 mg/kg/day for seven days, and the combined administration group. Rats that received gentamicin injections saw a fall in body weight along with a decrease in liver function and all hematological parameters except the white blood cell count. The tissue's total antioxidant capacity (TAC) dropped as a result of gentamicin, indicating oxidative stress. Gentamicin additionally caused histological alterations and significant increases in DNA fragmentation levels in the spleen and liver tissues. In contrast, the combined administration of gentamicin and Sarcophyton extract preserved body weight, maintained liver tissue structure and function, and improved hematological markers. Moreover, it strengthened the tissue's TAC, restored the normal structure of the spleen tissues, and decreased the tissue's DNA fragmentation. Sarcophyton's chemical components, identified using gas chromatography-mass spectrometry, have hepatoprotective, antioxidant, and anti-inflammatory qualities, which are responsible for the extract's ameliorative effects. Finally, Sarcophyton extract is a natural medication that may help reduce the toxicity caused by gentamicin.