Background: Natural bioactive compounds and nanomaterials are increasingly explored for their potential in managing metabolic disorders. This study investigated the effects of Spirulina platensis and silver nanoparticles (AgNPs) on lipid metabolism and liver enzyme activity in healthy and hyperlipidemic rats. Methods: The experiment was conducted between September and November 2021 at Tikrit University. Rats were divided into normal and hyperlipidemic groups and treated orally with Spirulina platensis (150 mg/ml), AgNPs (10 mg/ml), or their combination. Lipid profile parameters, including triglycerides, total cholesterol, Low-Density Lipoprotein (LDL), very Low-Density Lipoprotein (vLDL) and High-Density Lipoprotein (HDL), were assessed alongside liver enzymes AST, ALT and ALP. Results: Hyperlipidemia significantly disrupted lipid and hepatic parameters. In healthy rats, administration of AgNPs, Spirulina and their combination significantly reduced triglyceride levels compared to controls. In hyperlipidemic rats, these treatments markedly lowered triglycerides and total cholesterol relative to untreated diseased controls. Additionally, treated groups exhibited decreased LDL and vLDL levels, alongside increased HDL concentrations. Liver enzyme activities (AST, ALT, ALP) were significantly reduced in both treated healthy and hyperlipidemic groups, indicating improved hepatic function. The combined treatment generally produced the most pronounced beneficial effects. Conclusion: Oral administration of Spirulina platensis and silver nanoparticles, individually and synergistically, improves lipid profiles and liver enzyme status in both normal and hyperlipidemic conditions, highlighting their potential therapeutic value in managing hyperlipidemia.