Thanks to their simple synthesis, controlled physical properties, and minimal toxicity, iron oxide nanoparticles (FeO NPs) are widely used in many biomedical applications (e.g., bioimaging, drug delivery, biosensors, diagnostics, and theranostics). However, the use of NPs does not preclude the possibility of selective toxicity and undesirable effects, including accumulation in tissues and direct interaction with specific biological targets. This study evaluated the biocompatibility of FeO NPs, ( extract, rutin, and the corresponding complexes on the liver tissue of healthy white Wistar rats. The impact profile of the synthesized FeO NPs (15 ± 4 nm), rutin, extract, and their complexes on biochemical markers of liver function (ALT, AST, ALP, GGT, HDL, LDL, total cholesterol, total protein, and albumin) and morphological indicators of rat liver was investigated. FeO NPs, rutin, and extract do not show direct hepatotoxicity when administered intraperitoneally to rats, unlike their complexes. All agents exert a hypolipidemic effect by lowering LDL, despite maintaining the synthetic functions of the liver. FeO NPs increase the activity of GPO, which is associated with their peroxidase-like properties. A multifaceted and diverse mechanism of action of all studied samples on the liver of Wistar rats was identified.