The nuclear receptors PPAR gamma and PPAR alpha are therapeutic targets for insulin resistance/hyperglycemia and dyslipidemia, respectively.  Clinical successes of the single-action drugs that modulate these targets individually had drawn significant interest in a multi-targeted single-agent therapy to treat metabolic syndrome.  Moreover, with increased understanding of the role of PPAR delta for its dual benefit for both dyslipidemia and insulin resistance, potential synergistic effects of activating all three PPAR isoforms are of high interest.  Here we report a new class of PPAR triple agonists exemplified by the generic indoleacetic acid (I).  Through structure-activity relationship studies, in vivo characterizations, and ADME profiling, compounds with similar potency on glucose-lowering and lipid endpoints possessing favorable drug properties were identified.  Leads in this class normalize blood glucose while demonstrating lipid modulating effects in a diverse array of animal models.