Although aminoglycosides like amikacin have strong antibacterial properties, they also cause nephrotoxicity and hepatotoxicity. The point of this study was to find out how well curcumin (CR) and Nigella sativa (NS) herbal extracts protected rats from the liver and kidney damage that amikacin (AK) caused. The study involved 35 adult male albino rats, which were randomly and equally divided into 7 groups. Group 1 (G1) rats were injected intraperitoneally (IP) with normal saline and served as the negative control. In Group 2, rats were intraperitoneally injected with a dosage of 25 mg/kg body weight of AK for a duration of 7 days. In Group 3, rats were orally administered a dosage of 2 ml/kg body weight of NS daily for a duration of 14 days. Besides, in group 4, rats were orally administered a dosage of 200 mg/kg body weight of CR daily for a duration of 14 days. In group 5, rats were given NS one hour prior to AK treatment, but in group 6, rats were given CR one hour prior to AK administration. In group 7, rats were given both NS and CR one hour before AK treatment. The obtained results demonstrated elevated serum levels of ALT, AST, urea, creatinine, and malonaldehyde (MDA) in the AK groups. However, the levels of these markers significantly decreased when the rats were administered NS, CR, or a combination of both. The histological characteristics of the liver and kidney were enhanced following the administration of NS, CR, or a combination of both. Ultimately, the use of both CR and NS plays a defensive function in safeguarding the liver and kidney from the detrimental consequences of AK.