Spirulina platensis have therapeutic functions such as antioxidant, anti-bacterial, antiviral, anticancer, anti-inflammatory, anti-allergic and anti-diabetic. The purpose of this study was to evaluate the protective effect of spirulina platensis on L-methionine induced hyperhomocysteinemia (HHcy) in rats. Thirty male albino rats were divided into three equal groups. Group I (control normal): rats administered distilled water. Group II (hyperhomocysteinemic group (HHcy): rats received L-methionine (1.7 gm/kg body weight/day) orally for continuous 8 weeks. Group III (HHcy + spirulina platensis): rats received spirulina (1.5 gm/kg body weight/day) orally for 4 weeks after induction of hyperhomocysteinemia. The obtained results showed significant increase in serum homocysteine, lipids profile (total cholesterol and triacylglycerols), liver marker enzymes (ALT, AST and ALP), liver L-MDA and pro-inflammatory cytokines (TNF-α and IL-8) gene expression level in hyperhomocysteinemic (HHcy) rats. However, liver SOD activity and GSH concentration were markedly decreased. Spirulina treatment to L-methionine induced HHcy in rats caused significant improvement of all previous parameters towards its normal ranges. These results suggested that, spirulina treatment exerts a protective effect on HHcy by reduction of oxidative stress marker, inflammation and hyperhomocysteinemia in rats through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidant defense system mechanisms.