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Dietary supplements, including fatty acids (FAs), are recognized for their role in preventing many diseases. Extensive research in the last decade has established FAs, mainly polyunsaturated ones, as multi-therapeutic agents to treat several diseases ranging from inflammation to cancer. Such FAs have been reported to occur in a wide variety of foods of plant and animal origin. Inedible plants, amongst which those having folk medicinal value, represent an untapped source of FAs. Although the literature relating biological activities of plants to their FA content is limited, some studies have demonstrated anti-inflammatory, antibacterial, hypoglycemic, hypocholesterolemic and antitumor activities for several plant-derived FAs. On the other hand, omega (n)-3 polyunsaturated fatty acids (PUFAs) and conjugated linoleic acid (CLA), the most studied FAs, have been shown to resolve several ailments, including chronic inflammatory diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA) and inflammatory bowel disease (IBD). Indeed, long-term administration of marketable formulas containing these PUFAs exerts protective effects against different diseases. In addition, modification of dietary habits in favor of n-3 PUFAs and CLA provides an alternative means to maintain a healthy state. This chapter provides an overview of plant-derived FAs and their edible and inedible sources, summarizes the biological effects of plant-derived FAs and reviews the mechanism of action of n-3 PUFAs and CLA.