The present study investigated the therapeutic potential of omega-6 fatty acids, according to their effects on antioxidant markers and matrix metalloproteinases (MMPs), in coronary heart disease-induced rats. Rats were grouped into group I (sham control), group II (control), group III (0.5 g/kg bwt of omega-6 fatty acids) and group IV (1 g/kg bwt of omega-6 fatty acids). Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, glutathione peroxidase (Gpx) and acetylcholinesterase (AChE) enzyme activities were determined. ROS and MDA were substantially reduced, whereas SOD, catalase, Gpx and AChE were significantly increased, following supplementation with omega-6 fatty acids. MMP-2 mRNA expression was drastically increased by 95% in group II. Treatment significantly reduced MMP-2 mRNA expression by 12.3% and 26.7% in groups III and IV respectively. MMP-9 mRNA expression drastically increased, by 121%, in group II. Treatment significantly reduced MMP-9 mRNA expression by 22.6% and 29.4% in groups III and IV respectively. MMP-2 protein expression was drastically increased, by 81%, in group II. Treatment significantly reduced MMP-2 protein expression by 9.4% and 26% in groups III and IV respectively. MMP-9 protein expression was drastically increased, by 100%, in group II. Treatment significantly reduced MMP-9 protein expression by 18.9% and 26.9% in groups III and IV respectively. In summary, the consumption of omega-6 fatty acids significantly decreased MDA and ROS, while SOD, catalase, GHS, Gpx and AChE were increased. Furthermore, omega-6 fatty acids significantly downregulated MMP-2 and MMP-9 expression in our coronary heart disease-induced rat model.